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What gram staining is streptococcus

Gram + coccus
How does growth of strep and staph differ?
- Staph ? clusters of gram + cocci
- Strep ? gram + cocci grow along a single axis in pairs or long chains
What are group A strep

Strep pyogenes
What is the capsule of strep pyogenes made of?

Hyaluronic acid
What is special about hyaluronic acid capsule
- Hyaluronic acid is also found in our connective tissue
- Therefore, it is non immunogenic
What kind of hemolysis does strep pyogenes have?

Beta hemolytic
What kinds of infections can strep pyogenes cause?
- Pyogenic infections
- Toxin mediated
What pyogenic infections can strep pyogenes cause
- Impetigo
- Pharyngitis (strep throat)
- Cellulitis and erysipelas
What does impetigo look like?

Skin infection that looks honey crusted
What bacteria can cause impetigo
- Staph aureus
- Strep pyogenes
What does strep throat look like?

Red erythematous and inflamed throat
What is erysipelas

Superficial cellulitis with well demarcated borders
What is the most common cause of erysipelas?

Strep pyogenes
What toxin does strep pyogenes produce
- Streptococcal pyrogenic exotoxin (SPE)
- Streptolysin O
- Streptokinase
- DNases
what virulence factor mediates the beta hemolysis of strep pyogenes

streptolysin O ? lyses red blood cells
what antibodies do we create against strep pyogenes?

ASO ? Anti Streptolysin O antibodies
What does kinase mean

To add a phosphate
What does streptokinase do
- Converts plasminogen --> plasmin
- Plasmin is fibrinolytic (lyses clots)
What can we use streptokinase for in a medical medium?

To lyse clots in MI or ischemic strokes
What do DNases / Dornases do

Depolymerize DNA
How do we differentiate group A strep form Group B strep?
- Group A strep ? Bacitracin sensitive
- Group B strep ? Bacitracin resistant
How do we check if we have recently had a strep infection?

ASO antibody titers
What infections does streptococcal pyrogenic exotoxin cause
- Scarlet fever
- Toxic shock like syndrome
- Necrotizing fasciitis
What are the main symptoms of scarlet fever?
- Strawberry tongue ? reddening and swelling of tongue
- Pharyngitis
- Widespread rash that spares the face
What kind of toxins are pyrogenic exotoxin A and C and how does they work?
- Super antigen
- Causes nonspecific binding of MHC class 2 and T cell receptors --> over activation --> cytokine storm
- Could be fatal
What kind of toxin is pyrogenic exotoxin B?

Protease
What types of pyrogenic exotoxin exists?
- A ? super antigen
- B ? protease
- C ? super antigen
Which types of pyrogenic exotoxins are responsible for toxic shock like syndrome

A and C
Which types of pyrogenic exotoxins are responsible for scarlet fever

A and C
Which types of pyrogenic exotoxin are responsible for necrotizing fasciitis

B
What causes necrotizing fasciitis

Toxigenic strains of strep pyogenes
how does necrotizing fasciitis spread?
- invades the fascia underlying the skin
- spreads very rapidly
how do you treat necrotizing fasciitis?
- it is a true surgical emergency
- it is sometimes necessary to amputate the affected region
how do you treat strep infections?

penicillin
what are the serious complications of infections with strep pyogenes?
- Rheumatic Fever
- Post Streptococcal Glomerular Nephritis
What is the main virulence factor responsible for rheumatic fever?

M protein
What is M protein

Highly antigenic protein in strep pyogenes cell wall
How does M protein act as a virulence factor?
- Interferes with opsonisation ? anti-phagocytic
- Very antigenic ? elicits strong humoral response
What antigen resembles M protein

Self-antigen ? myosin in cardiac muscle
Through which process does M protein resemble myosin of the cardiac muscle

Molecular mimicry
What is the consequence of molecular mimicry in strep pyogenes infection?

Causes our own antibodies to attack our heart
Which valve is most commonly affected by rheumatic fever

Mitral valve
What problems does rheumatic fever cause for heart valves

Mitral stenosis
What disease does rheumatic fever occur after?
- Strep pharyngitis
- Never after skin infections
- Does not happen if pharyngitis is promptly treated
Who does rheumatic fever most commonly affect

Children who do not have access to good medical attention (the pharyngitis is not promptly treated)
What are the symptoms of rheumatic fever?
- J ? Joint ? polyarthritis
- <3 ? Heart ? valvular damage leading to murmurs, myocarditis, pericarditis
- N ? Nodules ? subcutaneous nodules that appear on extensor surfaces of forearms or elbows / knees
- E ? Erythema Marginatum ? rash with thick red borders
- S ? Sydenham?s Chorea ? rapid involuntary movements of hands and face
What are the Jones criteria?
- J ? Joint ? polyarthritis
- <3 ? Heart ? valvular damage leading to murmurs, myocarditis, pericarditis
- N ? Nodules ? subcutaneous nodules that appear on extensor surfaces of forearms or elbows / knees
- E ? Erythema Marginatum ? rash with thick red borders
- S ? Sydenham?s Chorea ? rapid involuntary movements of hands and face
What are the difference between rheumatic fever and post strep glomerulonephritis?
- Rheumatic fever
- type 2 hypersensitivity
- only after pharyngitis
- early diagnosis + treatment of pharyngitis can prevent development
- Post strep glomerulonephritis
- type 3 hypersensitivity
- occurs after pharyngitis or superficial infection (e.g. impetigo)
- early diagnosis + treatment of infection will not prevent development
How does strep pyogenes cause post strep glomerular nephritis?
- Type 3 hypersensitivity reaction
- Damage is mediated by circulating antibody ? antigen immune complexes that eventually deposit in the glomerulus
What are the main symptoms of post strep glomerular nephritis?
- Dark brown / cola colored urine
- Fascial swelling / puffiness from edema
How long does it take to develop post strep glomerular nephritis?

2 weeks after the initial strep infection
what diseases does post strep glomerular nephritis occur after
- pharyngitis
- superficial infections (e.g. impetigo)
how do you prevent post strep glomerular nephritis?

you can?t ? even when strep infection is treated promptly with penicillin this complication can still occur
What are the hemolytic properties of strep pneumoniae?

Alpha hemolytic
What does alpha hemolysis look like?

Surrounding zone of hemolysis is a green hue
Why is alpha hemolytic zone green

Due to oxidation of hemoglobin
What is strep pneumoniae capsule made of

Polysaccharide
What are the virulence factors of strep pneumoniae?
- Polysaccharide capsule
- IgA protease
What does IgA protease allow strep pneumoniae to do?

Colonies and invade mucosa
What does the capsule allow strep pneumoniae to do?

Evade immune system
How do you differentiate between strep pneumoniae and strep viridans?
- Strep pneumoniae
- optochin sensitive
- bile soluble (can?t grow in bile)
- encapsulated
- Strep viridans
- optochin resistant
- bile insoluble (grows on bile)
- unencapsulated
What shape is strep pneumoniae under high power microscopy

Lancet shaped gram + diplococci
What gram staining does strep pneumoniae have

Gram + coccus
Why can strep pneumoniae not grow on bile

It is bile soluble
What infections do strep pneumoniae cause
- M ? Meningitis
- O ? Otitis Media
- P ? Pneumonia
- S ? Sinusitis
What does MOPS stand for
- Infections for which strep pneumoniae is the most common cause
- M ? Meningitis
- O ? Otitis Media
- P ? Pneumonia
- S ? Sinusitis
What is the most common cause of community acquired pneumonia in adults?

Strep pneumoniae
What characteristic pneumonia does strep pneumoniae cause?
- Lobar pneumonia that infiltrates the lower lobes
- Causes rust colored sputum
Which population is at higher risk of being infected by encapsulated organisms

People who have undergone splenectomy or auto-splenectomy (e.g. in sickle cell disease)
Where are encapsulated organisms removed from the body

Spleen
How do we treat strep pneumoniae infection?
- Susceptible to Macrolides ? erythromycin
- 3rd generation cephalosporin ? ceftriaxone
How can we prevent strep pneumoniae infection?

2 pneumococcal vaccines available
How does the adult strep pneumoniae vaccine work?
- 23 valent polysaccharide vaccine
- T cell independent response generated
- This only creates IgM
- Not long lasting reaction
How does the child strep pneumoniae vaccine work?
- 7 valent conjugated to a protein
- Protein means it is more antigenic
- More robust T cell response
- IgG production
What are group B strep?

Strep agalactiae
Which group of people does strep agalactiae cause serious infections in

Newborns
What does hippurate in strep agalactiae do

Hydrolysis sodium hippurate
What is strep agalactiae?s capsule made of

Polysaccharide
How do we distinguish strep agalactiae from all other streps?

CAMP test
What is the CAMP test?
- When strep agalactiae is plated with staph aureus there is an increased zone of hemolysis
- Butterfly hemolytic zone
What are strep agalactiae hemolytic properties

Beta hemolytic
How do we differentiate strep pyogenes and strep agalactiae from strep pneumoniae and strep viridans?
- Strep agalactiae + strep pyogenes ? beta hemolytic
- Strep pneumoniae + step viridans ? alpha hemolytic
How do we differentiate strep agalactiae from strep pyogenes?
- Strep agalactiae ? bacitracin resistant
- Strep pyogenes ? bacitracin sensitive
What infections does strep agalactiae cause
- Meningitis in neonates
- Sepsis in neonates
- Pneumonia
What is the main cause of meningitis in neonates?

Strep agalactiae
How do neonates get strep agalactiae infections?

When the neonate passes through the vaginal canal of the mother during delivery
What prenatal care do we have to prevent neonatal strep agalactiae infections

Swab vagina and rectum of mother at 35 weeks to see if she is colonized
If mother is colonized with strep agalactiae how do we prevent strep agalactiae infection in neonate

Prophylactic Intrapartum penicillin administered to the mother
What are the hemolytic properties of strep viridans?

Alpha hemolytic
What gram staining does strep viridans have

Gram + coccus
Strep viridans capsule

Unencapsulated
What bacteria are found in the strep viridans group
- Strep mutans
- Strep sanguinis
What diseases do strep viridans cause
- Dental carries
- When passed into blood --> Subacute endocarditis and damaged heart valves
Which heart valve is most affected by bacteremic strep viridans infection
- Damaged heart valves ? Mitral valve
- Mitral valve prolapses very common + rheumatic fever affects mitral valve more
How do strep viridans affect heart valves?
- Previously damaged heart valve (mitral valve prolapse)
- Teeth cleaning --> strep viridans bacteria enter the blood stream --> transient bacteremia
- Strep viridans able to adhere any fibrin platelet aggregates at damaged tissue via dextrans
What are strep viridans virulence factors

Dextrans ? stick to platelets
How are dextrans formed

Formed by strep viridans from glucose
What does the name Enterococcus tell us?
- Entero = inhabits intestinal tract
- Coccus = cocci (not Enterobacter = rod)
What species are in the enterococcus genus
- E. faecalis
- E. faecium
Which species is more common in the enterococcus genus

E. Faecalis
Which species is more serious in the enterococcus genus

E. Faecium
What medium are enterococci able to grow in
- 6.5% NaCl
- Bile resistant so can grow on bile
What infections do enterococci cause?
- UTI
- Endocarditis
- Biliary tree infections
E. Faecium resistance
- To almost all antibiotics
- Including vancomycin
What kind of infection is E. Faecium?

Nosocomial
What does VRE stand for

Vancomycin Resistant Enterococcus
How do you treat VRE?
- Linezolid ? expensive big gun antibiotic
- Tigecycline ? expensive bug gun antibiotic
What does the name staphylococcus aureus tell us?
- Staph = grape (Latin)
- Coccus = granule (Latin)
- Look like bunch of grapes under microscope
- Aureus = golden (Greek)
- When grows on blood agar, colonies have yellow or golden appearance to them
What gram staining is Staph Aureus

Gram + coccus (take up crystal violet in thick cell wall and hold on to it even after rinse and addition of red safranin)
How do you tell the difference between staph and strep?

Catalase test ? + in staphylococci
What does catalase do?

Convert hydrogen peroxide to water
How to tell the difference between staph aureus and other staph?
- Golden color when plated
- Coagulase test
- Beta hemolytic
- Grow on mannitol salt agar
What is coagulase
- An enzyme that converts fibrinogen --> fibrin
- Present in staph aureus
What does beta hemolysis look like on a petri dish?

Glowing halo of light on a red backdrop
What is special about mannitol salt agar
- salt selects only staph species
- see if it ferments mannitol ? positive (pink --> yellow) ? staph aureus
what is the main virulence factor for staph aureus?

Protein A
How does protein A work
- Protein A is a component of staph aureus cell wall
- Binds the Fc portion of immunoglobulins
- This prevents compliment from binding to the Fc region
- Prevents opsonisation and phagocytosis
- Allows it to better colonize its host
Where does staph aureus colonize

Nares
What types of diseases does staph aureus cause?
- Infectious
- Toxin mediated
What infectious diseases does staph aureus cause?
- Pneumonia
- Skin infections
- Septic arthritis
- Endocarditis
- Osteomyelitis
What is typical of the pneumonia caused by staph aureus?
- See patchy infiltrates on X ray
- Usually a secondary post viral superinfection (after immune system has been weakened)
What is the most common cause of septic arthritis in adults?

Staph aureus
What kinds of skin infections does staph aureus cause?
- Cellulitis
- Impetigo
- Furuncles ? boils
- Carbuncles ? slightly larger boils
- Abscesses
What kind of endocarditis does staph aureus cause?
- Rapid onset (acute) bacterial endocarditis
- Usually in an IV drug user ? right sided infection on tricuspid valve
What is the most common cause of osteomyelitis in adults?

Staph aureus
What toxin mediated diseases does staph aureus cause?
- Scalded skin syndrome
- Toxic shock syndrome
- Food poisoning
What mediates scalded skin syndrome

Exfoliative toxin ? protease
What is the classic situation for someone getting toxic shock syndrome?

Someone leaving a foreign packing in for too long (gauze after rhinoplasty / tampon)
What kind of toxin is toxic shock syndrome toxin and how does it work
- Super antigen
- Causes nonspecific binding of MHC class 2 and T cell receptors --> over activation --> cytokine storm
- Could be fatal
What kind of food poisoning does staph aureus cause?
- Rapid onset due to preformed toxin (1-8 hours)
- Usually associated with vomiting more than diarrhea
- Associated with meats and mayonnaise etc.
What does MRSA stand for?

Methicillin Resistant Staph Aureus
How does MRSA become resistant?

Altering its Penicillin Binding Proteins
What does Penicillin Binding Protein do?

Helps build the cell walls
How do you treat MRSA?

Vancomycin
How do you treat staph aureus infection?
- Determine if it is methicillin sensitive
- If it is should use penicillin as it is more effective in killing bug
- Nafcillin = Naf for Staph
What gram staining is staph epidermidis

Gram + coccus ? takes up a lot of crystal violet stain
What does staph epidermidis often infect
- Implanted hardware
- Artificial joints
- Indwelling catheters
- Artificial heart valves (endocarditis)
Why is staph epidermidis called this way

Covers all of our skin
In what situation will staph epidermidis cause infections

When the skin is penetrated
How does staph epidermidis easily infect implants etc.?

Produces copious adherent biofilm which sticks to sleek metal and plastic surfaces
What is biofilm made of

Mesh of polysaccharides
What does biofilm do
- Helps bacteria stick to surfaces
- Acts as a coating that protects bacteria from antibiotics and immune cells
Why is staph epidermidis resistant to many antibiotics

The biofilm provides it with a protective coating
How do you treat staph epidermidis?
- Vancomycin for endocarditis
- Should replace any implants that are infected
Why is staph epidermidis often found in blood cultures

Part of the normal skin flora so easily contaminates cultures
How can you differentiate staph epidermidis from staph saprophyticus?
- Staph epidermidis is novobiacin sensitive
- Staph saprophyticus is novobiacin resistant
What gram staining is staph saprophyticus

Gram + coccus ? takes up a lot of crystal violet stain
What diseases does staph saprophyticus commonly cause

UTI ? in sexually active females
What features do staph epidermidis and staph saprophyticus have in common
- Catalase positive
- Urease positive
- Coagulase negative
how do you differentiate between staph aureus and staph saprophyticus or staph epidermidis?
- staph aureus ? coagulase positive
- staph epidermidis / saprophyticus ? coagulase negative
What does urease do

Converts urea into ammonia
What bacteria are urease positive
- Proteus
- Klebsiella
- Staph epidermidis
- Staph saprophyticus
what species are in the Neisseria genus
- Neisseria meningitidis
- Neisseria Gonorrhea
What gram staining are Neisseria

Gram ? diplococci
What biochemical properties do Neisseria have?

Oxidase +
How do you grow Neisseria?
- Chocolate agar
- VPN agar = Thayer martin agar
What do Neisseria species look like when grown on blood agar?

Unable to grow on blood agar
Why are Neisseria unable to grow on blood agar

Inhibited by some of the lipids and other elements in blood agar
What is chocolate agar

Heated blood agar
Why do we use chocolate agar to culture Neisseria?

Heating inactivates the inhibitors to growth found in blood agar
What is VPN agar

Agar enriched with vancomycin + polymyxins + nyastin
What is another name for VPN agar?

Thayer martin agar
Wo is more susceptible to Neisseria infections

Compliment deficiency of C5 ? C9
What does compliment deficiency of C5-C9 cause

Unable to form Membrane Attack Complex (MAC) --> increase susceptibility to Neisseria infections
What are the virulence factors of Neisseria?
- Pilus
- IgA protease
What is the function of Neisseria pili?
- Attachment to mucosal surfaces
- Frequent genetic rearrangement --> antigenic variation
What does the antigenic variation of Neisseria mean for our immune system?
- Difficult to target
- Prevents any lasting immune response
How does Neisseria evade our immune system?

Antigenic variation of pili through frequent genetic rearrangements
What is IgA protease

Protein that cleaves IgA at its hinge point
What does IgA protease do?
- Cleaves IgA at its hinge point
- Facilitates survival along mucosal surfaces
How do Neisseria survive on mucosal surfaces?

IgA protease
What gram stain is Neisseria

Gram ? diplococci
What biochemical properties does Neisseria have?

Oxidase positive
How do you grow Neisseria?
- Chocolate agar
- VPN agar = Thayer martin agar
Who is susceptible to Neisseria infections?

C5-C9 compliment deficient patients due to inability to form MAC complex
What virulence factors does Neisseria meningitidis have
- IgA protease
- Pili that demonstrate antigenic variation
- Polysaccharide capsule
How is Neisseria meningitidis spread

Respiratory droplets
Where is Neisseria meningitidis spread

Close quarters ? e.g. dorms
What differentiates Neisseria meningitidis from Neisseria gonorrhea
- Ferments glucose and maltose (Meningitidis)
- Only ferments glucose (gonorrhea)
- Encapsulated (meningitidis)
- Non encapsulated (gonorrhea)
How does Neisseria meningitidis infection occur

Respiratory droplets --> colonize nasopharynx -->hematogenous spread
What is the Neisseria meningitidis capsule made of?

Polysaccharide
What is the function of the Neisseria meningitidis capsule?

Inhibits phagocytosis
What kind of vaccine is used for Neisseria meningitidis?

Contain polysaccharide capsule (types A, C, D)
Which polysaccharide capsules are included in the Neisseria meningitidis vaccine
- A, C, D
- NOT B
Which strain of Neisseria meningitidis causes most infections in developed world and why

B because it is not included in the vaccine
Who is most susceptible to Neisseria meningitidis infections
- Sickle cell anemia
- Asplenic patients
Who more susceptible to infections caused by encapsulated organisms
- Sickle cell anemia
- Asplenic patients
Which organisms are asplenic patients more susceptible to
- Encapsulated organisms
- * Streptococcus pneumoniae
- * Haemophilus influenzae
- * Neisseria meningitidis
What happens when Neisseria meningitidis enters the blood stream
- Massive inflammatory response --> increased permeability of capillaries --> leakage of fluid into extravascular space --> hypovolemic shock --> peripheral vasoconstriction --> adrenal insufficiency --> farther exacerbation of shock
- Thrombocytopenia --> Characteristic petechial rash
What causes the massive inflammatory response to hematogenous Neisseria meningitidis?

Lipoolygosaccharides (LOS) outgrows surface of bacteria --> blebs off
What is LOS

LipoOligoSaccharide envelope protein of Neisseria meningitidis
What does petechial rash suggest in a patient?

Thrombocytopenia
What is DIC

Disseminated Intravascular Coagulation
What are the early signs of DIC?

Petechial rash --> purpura --> ecchymosis
What would you see in a physical exam of a patient with DIC?
- Oozing at the venipuncture sites
- Bleeding gums
What causes waterhouse frederichson syndrome
- Neisseria meningitidis
- Massive inflammatory response to LOS --> Hypovolemic shock --> peripheral vasoconstriction
What is waterhouse Frederichson syndrome

Adrenal infarction due to Neisseria meningitidis infection
What are the general stages of Neisseria meningitidis infection?
- Nasopharyngeal colonization
- Hematogenous spread (meningeal symptoms)
- Hypovolemic shock + DIC
- Waterhouse frederichson syndrome
How do you treat Neisseria meningitidis infection?
- 3rd generation cephalosporin that can penetrate the blood brain barrier
- Ceftriaxone
- Prophylactic treatment of close contacts with rifampin
Why do we give prophylaxis to close contacts in Neisseria meningitidis infection?
- Spread by respiratory droplets
- Highly contagious
What is defined as a ?Close contact? in Neisseria meningitidis infection

Someone who has spent over 8 hours with the patient during the 7 days prior to onset
What is the prophylaxis for Neisseria meningitidis infection?

Rifampin
What gram stain is Neisseria

Gram ? diplococci
What biochemical properties does Neisseria have?

Oxidase positive
How do you grow Neisseria?
- Chocolate agar
- VPN agar = Thayer martin agar
Who is susceptible to Neisseria infections?

C5-C9 compliment deficient patients due to inability to form MAC complex
What virulence factors do Neisseria have
- IgA protease
- Pili that demonstrate antigenic variation
What differentiates Neisseria meningitidis from Neisseria gonorrhea
- Ferments glucose and maltose (Meningitidis)
- Only ferments glucose (gonorrhea)
- Encapsulated (meningitidis)
- Non encapsulated (gonorrhea)
What kind of infection is gonorrhea?

STD ? Sexually Transmitted Disease
where can Neisseria gonorrhea grow

facultative intracellular
what cells does Neisseria gonorrhea invade?

polymorphonuclear lymphocytes (PMN)
what is the area that Neisseria gonorrhea most commonly affects?

genetelia of men and women
what can Neisseria gonorrhea cause in men
- urethritis --> prostatitis --> orchitis
- polyarthritis
what can Neisseria gonorrhea cause in women
- urethritis --> pelvic inflammatory disease (PID) --> spread into peritoneum
- polyarthritis
what is PID

Pelvic inflammatory disease
What can PID cause

Scarring --> infertility / atopic pregnancies
What does Neisseria gonorrhea urethritis look like?

Thick white purulent discharge
What does chlamydia trachomatis urethritis look like?

Thin watery purulent discharge
What are the main causes of urethritis?
- Chlamydia trachomatis
- Neisseria gonorrhea
What is Fitz Hugh Curtis syndrome?

Neisseria gonorrhea infection spreading into peritoneum
What can Fitz Hugh Curtis syndrome cause

Violin string adhesions ? adhesions to the capsule of the liver (long + thin)
Where does Neisseria gonorrhea polyarthritis occur

Knee ? often asymmetric
Who does Neisseria gonorrhea affect

Young sexually active people
How do you diagnose Neisseria gonorrhea polyarthritis?

Joint tap with purulent synovial fluid that doesn?t gram stain
Why is gram stain ineffective in diagnosis of Neisseria gonorrhea?

Intracellular
How do we get congenital Neisseria gonorrhea infection?

Expecting mother with untreated gonococcal infection passes it to child during delivery
How will congenital Neisseria gonorrhea infection manifest

Purulent conjunctivitis that occurs within first 5 days of life
How will congenital chlamydia trachomatis infection manifest

Purulent conjunctivitis that occurs a week after birth
What are the main differences between Neisseria gonorrhea and chlamydia trachomatis infections?
- Urethral discharge is thick and very purulent (gonorrhea)
- Urethral discharge is thin and watery (chlamydia)
- Neonatal conjunctivitis occurs within first 5 days of life (gonorrhea)
- Neonatal conjunctivitis occurs after 1 week of life (chlamydia)
How do we treat Neisseria gonorrhea infection?
- Ceftriaxone (gonorrhea)
- Macrolides ? azithromycin / doxycycline (chlamydia co infection)
Why do we treat patients with more than one antibiotic?

Chances of co infection with chlamydia trachomatis are very high so we should treat both in case
What gram stain is Brucella

Gram ? coccobacillus
Where can we find Brucella

Zoonotic ? associated with cattle and other farming animals
What is the reservoir for Brucella?

Farm animals ? cows / sheep / goats / pigs
What species are there in Brucella genus?
- Different species for different animals
- Cow ? Brucella bordis
Who is affected by Brucella infections
- Direct contact with animals ? people with direct contact with animals
- * Veterinarian
- * Slaughter house workers
- * Rancher
How is Brucella transmitted
- Direct contact with animals
- Indirect contact by consumption of milk / chees products
Where can Brucella grow
- Facultative intracellular
- Inside cells such as macrophages
How do Brucella survive intracellularly in macrophages?

Prevent phagolysosome fusion
What does Brucella cause

Brucellosis
What is the clinical presentation of brucellosis?
- Primary symptoms ? non specific
- * Undulant fever
- * chills
- * anorexia
- enlargement of reticuloendothelial organs (spleen / liver / lymph nodes)
- osteomyelitis
what is undulant fever
- pattern of fever that rises and falls
- can be caused by brucellosis
where can Brucella spread in the body and why

able to survive in macrophages and be carried to multiple organs in reticulo endothelial system
what is the pathogenesis of brucellosis?
- Brucella is taken up by macrophages
- Prevents phagolysosome fusion
- Replicates intracellularly until host cell lyses
- Spread systemically
Which organs are part of the reticulo endothelial system
- Spleen
- Liver
- Lymph nodes
What is a complication of chronic brucellosis?

Osteomyelitis
How do we treat brucellosis?

Tetracycline (doxycycline) AND rifampin
What gram stain is Francisella tularensis

Gram ? coccobacillus
What does Francisella tularensis cause

Tularemia
Where can we find Francisella tularensis

Zoonotic ? rabbits
What is the main reservoir for Francisella tularensis?

Rabbits
How is Francisella tularensis transmitted
- Direct contact with rabbits ? handling rabbits / eating rabbit meat
- Indirect contact ? tick vector
- Aerosolized
Which tick transmits Lyme disease caused by Borrelia burgdorferi

Ixodes tick
Which tick transmits Francisella tularensis

Dermacentor tick
Why is Francisella tularensis possible to use in bioterrorism

Can be aerosolized
What shape is Francisella tularensis

Coccobacillus
Where can Francisella tularensis grow

Facultative intracellular
Which kind of immunity is important for recovery from Francisella tularensis infection

Cell mediated immunity (intracellular organism)
What is the pathogenesis of Francisella tularensis infection?
- Tick bites human
- Bacteria enters at site of bite --> painful ulcer
- Enters macrophages
- Travels through lymph system --> reticuloendothelial organs
What is the clinical presentation of tularensis?
- Painful ulcer at tick bite site
- Granulomas with caseating necrosis in reticuloendothelial organs (lymph nodes)
- Regional lymphadenopathy
- How do we treat Francisella tularensis infection?
- Aminoglycosides ? streptomycin
What does Bordetella pertussis infection cause?

Whooping cough
What gram stain is Bordetella pertussis

Gram ? coccobacillus
How is Bordetella pertussis transmitted?

Respiratory droplets
How does Bordetella pertussis cause infection?
- Attaches to respiratory epithelium using pili
- Releases toxins to cause systemic effects
What are virulence factors of Bordetella pertussis?
- Pilli ? filamentous hemagglutinin
- Toxins
- * Pertussis toxin
- * Adenylate cyclase toxin
- * Tracheal toxin
What does Bordetella pertussis use filamentous hemagglutinin for?

Attaching to respiratory epithelium
What is the name of Bordetella pertussis pili?

Filamentous hemagglutinin
How does Bordetella pertussis cause systemic effects?

Releasing toxins after attaching to respiratory epithelium
What do antibodies target in Bordetella pertussis?

Filamentous hemagglutinin pili
Which toxins does Bordetella pertussis have
- Pertussis toxin
- Adenylate cyclase toxin
- Tracheal toxin
How does Bordetella pertussis work?
- ADP ribosylation of Gi (inhibitory G) protein --> Gi is inhibition --> rise in cAMP
- Also disables chemokine receptors for lymphocytes --> Lymphocytes unable to enter lymphoid tissue --> stuck in blood stream --> massive lymphocytosis
What is the function of Gi protein?
- Inhibitory G protein
- Inhibits cAMP formation
What causes massive lymphocytosis in Bordetella pertussis

Pertussis toxin disables chemokine receptors for lymphocytes
How does

Acts as an adenylate cyclase --> Increases cAMP levels
What do Bordetella pertussis and Bacillus anthracis have in common?
- Adenylate cyclase toxin (Bordetella pertussis)
- Edema factor (Bacillus anthracis)
How does tracheal toxin work?
- Damages ciliated cells in respiratory epithelium
- Cleaves cilia
Where do we find tracheal toxin?

Part of peptidoglycan wall of Bordetella pertussis
What is the target for tracheal toxin?

Ciliated cells in respiratory epithelium
Who is most affected by Bordetella pertussis infection

Children
What is the clinical presentation of Bordetella pertussis infection?
- Catarrhal phase ? Initially nonspecific symptoms (1-2 weeks)
- Paroxysmal phase ? whooping cough (2 weeks ? 2 months)
- Convalescent phase ? gradual reduction in symptoms (up to 3 months)
How long does the catarrhal phase of Bordetella pertussis infection last?

1-2 weeks
What is the clinical presentation of the catarrhal phase of Bordetella pertussis infection?
- Nonspecific symptoms
- * Conjunctival injection
- * Lacrimation
- Lasts 1-2 weeks
How long does the paroxysmal phase of Bordetella pertussis infection last?

2 weeks ? 2 months
What is the clinical presentation of the paroxysmal phase of Bordetella pertussis infection?

Intense bouts of coughing that get children so out of breath that when eventually breath in it makes characteristic whooping sound on inspiration
How long does the convalescent phase of Bordetella pertussis infection last?

Up to 3 months
What is the clinical presentation of convalescent phase of Bordetella pertussis infection?

Gradual reduction in symptoms
What is another way to call whooping cough and why?
- 100-day cough
- Lasts for a very long time with phases going on for months
How do we treat Bordetella pertussis infection?
- Macrolides ? remove bacteria in the respiratory tract
- Vaccination
Why is it important to start treatment early in Bordetella pertussis infection?
- Macrolides can remove the bacteria but do not affect the toxins already circulating in the body
- So macrolides are ineffective in symptom improvement
What kind of vaccines do we have for Bordetella pertussis?
- Killed vaccine ? no longer in use
- Acellular vaccine
What is the acellular vaccine for Bordetella pertussis made of?

Purified antigens
What is DPT
- Vaccine given to children
- Diphtheria toxoid
- Pertussis antigens
- Tetanus toxoid
What gram stain is Haemophilus influenzae

Gram ? coccobacillus
What shape does Haemophilus influenzae have

Coccobacillus
How do we grow Haemophilus influenzae?

Chocolate agar with Factor 5 (NAD) and Factor 10 (hematin)
What is factor 5

NAD
What is factor 10

Hematin (hema-ten)
Which bacteria required factor 5 + 10 to grow

Haemophilus influenzae
How is Haemophilus influenzae transmitted

Aerosol transmission
What does Haemophilus influenzae infection cause
- Pneumonia
- Epiglottitis
- Otitis media
- Meningitis
- Sepsis
- Septic arthritis
What is a common causes epiglottitis?

Haemophilus influenzae
What is the clinical presentation of epiglottis caused by Haemophilus influenzae?
- Inflamed epiglottis ? cherry red epiglottis
- Inspiratory stridor
- Drooling
Who is most affected by epiglottitis caused by Haemophilus influenzae

Children
What is otitis media

Inflammation of the middle ear
Which form of Haemophilus influenzae causes meningitis

Type B capsular strain
Who is most affected by septic Haemophilus influenzae infections
- Asplenic patients
- Sickle cell patients
What is the function of the spleen in relation to bacteria?

Remove encapsulated organisms
Why is Haemophilus influenzae meningitis rare in the USA

Successful vaccination efforts
What kind of vaccine is vaccine for Haemophilus influenzae?

Polysaccharide capsular antigen (type B) conjugated to the diphtheria toxoid
Why do we have conjugated vaccines?
- Proteins increase antigenicity of capsular polysaccharide
- Body produces strong IgG response
When do we vaccinate for Haemophilus influenzae?

2-18 months
How do you treat Haemophilus influenzae?
- Beta lactams
- Meningitis / systemic disease ? ceftriaxone
- Prophylaxis for meningitis ? rifampin
How do we treat Haemophilus influenzae meningitis?

Ceftriaxone
what do you use for prophylaxis of Haemophilus influenzae in close contacts?

rifampin
What gram stain is Listeria monocytogenes

Gram + bacillus
What is Listeria monocytogenes most associated with?

Infections in pregnant women
What are listerias hemolytic properties

Beta hemolytic with narrow zone of hemolysis
Where can Listeria grow

Facultative intracellular organism
What does listeria use its flagella for?

Tumbling motility when it is extracellular
How does listeria move intracellularly?
- Actin rockets ? rapidly polymerizes actin against the bacteria wall so that it is propelled along in opposite direction
- Can be from cell to cell
How does listeria move from cell to cell?

Through actin rocket propulsion across cell membranes
What biochemical markers does listeria have?

Catalase + (like staph)
Why are listeria able to contaminate food items

Able to survive and multiply in near freezing temperatures ? contaminates refrigerated items
What kind of food does listeria contaminate?
- Unpasteurized milk
- Packages meat
- Soft cheeses
Who does listeriosis affect most

Pregnant women ? 20x more likely
What does listeriosis during pregnancy cause
- Early in pregnancy ? termination
- Later in pregnancy ? diseases in the newborn
How do we decrease likelihood of getting listeriosis in pregnant women?

Discouraged from eating unpasteurized products and soft cheeses
What diseases does listeria monocytogenes cause?

Meningitis in newborns and adults over 60
What are the 3 most common causes of meningitis in newborns
- Group B strep
- E. coli
- Listeria Monocytogenes
What is the standard empirical treatment for meningitis in adults?
- Vancomycin (gram +)
- AND Ceftriaxone (gram -)
- What is the treatment for meningitis in adults over 60?
- Vancomycin (gram +)
- AND Ceftriaxone (gram -)
- And Ampicillin (listeria)
How do we treat listeriosis?

Ampicillin
What are the gram staining properties of Corynebacterium?

Gram + rod (club shaped)
What does Corynebacterium diphtheriae cause

Diphtheria
What does Corynebacterium diphtheria look like?
- Club shaped ? Y or V formation
- Contains metachromatic granules
How do you stain metachromatic granules?

Aniline dyes
What toxin does Corynebacterium diphtheria produce?

Diphtheria Exotoxin
What is the structure of Corynebacterium diphtheria exotoxin?
- 2 subunits A and B
- A ? Active
- B ? Binding
What does Corynebacterium diphtheria exotoxin do?

Causes ADP ribosylation of elongation factor 2 --> inhibits ribosome function --> inhibits protein synthesis cell death
What is a pseudomembrane of the oropharynx

Thick greyish exudate over the mucosal surface
What bacteria causes a pseudomembrane in the oropharynx

Corynebacterium diphtheriae
What bacteria cause pseudomembrane formation
- Corynebacterium diphtheriae
- Clostridium difficile
Where are Corynebacterium diphtheriae psuedomembranes formed

Throat and tonsils (oropharynx) --> larynx --> trachea
How is Corynebacterium diphtheriae infection transmitted

Respiratory droplets
What symptoms does Corynebacterium diphtheriae cause?
- Airway obstruction (when spread to larynx and trachea)
- Bulls neck ? severe lymphadenopathy with characteristic thickening of the neck
What causes bulls neck

Corynebacterium diphtheriae lymphadenopathy --> thickening of the neck
When causes systemic effects of Corynebacterium diphtheriae infection

Exotoxin going into bloodstream
What systemic effects can Corynebacterium diphtheriae infection cause
- Cardiotoxic effects
- * Life threatening myocarditis
- * Arrhythmias
- * Heart block
- Neurotoxic effects
- * Local paralysis that begin in the posterior pharynx --> other cranial nerve deficits
What life threatening effects does Corynebacterium diphtheriae have

Life threatening myocarditis
How does diphtheria exotoxin cause neurogenic effects?

Damages myelin of nerve fibers
How do you definitively diagnose Corynebacterium diphtheriae infection?
- Good clinical history + physical exam ? gives a good idea but not definitive
- Culturing
- Toxin assay
how do you grow Corynebacterium diphtheriae?
- Tellurite media
- Loeffler?s media
How do you differentiate between toxic and nontoxic strains of Corynebacterium diphtheriae?

ELEKs test
How does ELEKs test work
- In vitro assay on filter paper that has antitoxin on it
- If toxin binds on it there is a reaction --> strain is toxic
What is ELEKs test used for

Differentiating between toxic and nontoxic strains of Corynebacterium diphtheriae
Which population is at greater risk of getting diphtheria

Unvaccinated (immigrant) children
What kind of vaccine is Corynebacterium diphtheriae vaccine?

Toxoid vaccine
What is a toxoid vaccine?

Consists of inactivated exotoxin bound to protein
What kind of immune response do we get from toxoid vaccines

Powerful IgG response
What is DPT vaccine
- Diphtheria ? toxoid vaccine (Corynebacterium diphtheriae)
- Pertussis ? acellular vaccine (Bordetella pertussis)
- Tetanus ? toxoid vaccine (Clostridium tetani)
How do you treat diphtheria?
- Preventative vaccination
- Passive immunization
What is passive immunization

Administering antitoxoid
What gram stain is Escherichia coli

Gram ? rod (enterobactericiae)
What bacteria are part of the Escherichia coli group
- EHEC ? Entero Hemorrhagic
- ETEC ? Entero Toxigenic
- EPEC ? Entero Pathogenic
- EIEC ? Entero Invasive
What biochemical properties do Escherichia coli have?
- Ferment lactose
- Catalase +
How do you test for lactose fermentation?

Grow pink on MacConkey agar
Which bacteria are lactose fermenters
- Klebsiella
- Enterobacter
- Serratia
- Escherichia coli
What are Escherichia coli virulence factors?
- Capsule
- Fimbriae
- LipoPolySaccharide (LPS) endotoxin
What is Escherichia coli capsule made of?

K antigen
What do we use to serotype Escherichia coli?

K antigen of the capsule
What is EMB agar

Eosin Methylene blue agar
how does Escherichia coli look on EMB agar?

metallic green sheen
what is necessary for Escherichia to cause urinary tract infection

fimbriae
what does Escherichia coli infection cause?
- urinary tract infection (UTI)
- sepsis
- meningitis in neonates
what is the number one cause of urinary tract infection?

Escherichia coli
What is the number one cause of gram ? sepsis

Escherichia coli
What is the virulence factor important for causing Escherichia coli sepsis?

Lipopolysaccharide (LPS) endotoxin
What does Escherichia coli endotoxin cause?

Sepsis
Where is Escherichia coli endotoxin located
Outer cell membrane
- What is a common virulence factor for all gram ? bacteria
- Lipopolysaccharide (LPS) endotoxin
What virulence factor must be present for Escherichia coli to cause meningitis in neonates

K capsular antigen
How is Enterohemorrhagic Escherichia coli most commonly transmitted

Undercooked meat (e.g. hamburgers)
What does Enterohemorrhagic Escherichia coli infection cause
- Bloody diarrhea
- Hemolytic uremic syndrome (HUS)
How can you differentiate Enterohemorrhagic Escherichia coli from other E. coli?

Does not ferment sorbitol
What are Enterohemorrhagic Escherichia coli virulence factors
- Capsule
- LPS endotoxin
- Fimbriae
- Shiga like toxin
What toxin does Enterohemorrhagic Escherichia coli secrete

Shiga like toxin
How does shiga like toxin cause damage

Inhibits ribosomes at the 60S position
What can shiga like toxin cause
- Tissue damage
- Hemolytic Uremic Syndrome (HUS) in children under 10
What is the pathogenesis of hemolytic uremic syndrome?
- Shiga (like) toxin damages endothelial cells of the capillaries in the glomerulus
- Damaged endothelial lining becomes thrombogenic --> platelets adhere
- Clumps of platelets lyse red blood cells as they pass through capillaries
Which Enterohemorrhagic Escherichia coli serotype causes massive outbreaks

O157 H7
What is O157 H7

Enterohemorrhagic Escherichia coli strain known to cause massive outbreaks
What does Enterotoxigenic Escherichia coli infection cause

Travelers diarrhea
How is Enterotoxigenic Escherichia coli transmitted

Water sources
Where is Enterotoxigenic Escherichia coli commonly found

Mexico in the water
What virulence factors does Enterotoxigenic Escherichia coli have
- Capsule
- Fimbriae
- LPS endotoxin
- Heat labile toxin
- Heat stable toxin
Which toxins does Enterotoxigenic Escherichia coli secrete
- Heat labile toxin
- Heat stable toxin
How does Enterotoxigenic Escherichia coli heat labile toxin work

Increases cAMP
How does Enterotoxigenic Escherichia coli heat stable toxin work

Increase cGMP
Which Enterotoxigenic Escherichia coli and Vibrio cholerae toxins are similar
- Heat labile toxin (Enterotoxigenic Escherichia coli)
- Cholera toxin (Vibrio cholerae)
- Both increase cAMP
What is the clinical presentation of Enterotoxigenic Escherichia coli infection?

Watery diarrhea
What gram stain is salmonella

Gram ? rod (Enterobacteriaceae)
What virulence factors does salmonella have
- Motile
- Encapsulated
- Facultative intracellular (macrophages)
What is a common feature of all motile Enterobacteriaceae?

H2S +
How do we test for H2S positivity?

Black colonies on Hektoen enteric agar
What biochemical properties do salmonella have?
- Acid labile
- H2S +
Why are do you need a high dose of salmonella to cause infection

Acid labile ? easily degraded in the stomach
Which Enterobacteriaceae requires high doses to cause infection

Salmonella (1,000 organisms to cause infection)
Which Enterobacteriaceae requires very low dose to cause infection

Shigella (10-100 organisms to cause infection)
Who is more susceptible to salmonella infection
- Patients with lowered stomach acidity
- * Omeprazole (treatment for reflux)
- * Pernicious anemia
How do salmonella infections progress?

Ingested --> stomach --> small intestine --> colon --> lymphatics --> taken up by macrophages --> blood
What is the reservoir for salmonella typhi?
- Gallbladders of chronic carriers
- What does salmonella typhi infection cause
- Enteric fever ? typhoid fever
- Osteomyelitis in patients with sickle cell disease
What is the clinical presentation of enteric fever?
- Rose colored macules on abdomen (25% of patients)
- Usually constipation
- Can be diarrhea ? pea soup colored
What is the number one cause of osteomyelitis in patients with sickle cell disease?

Salmonella typhi
How do we treat salmonella typhi infection?
- Fluoroquinolones
- Vaccination
What kind of vaccine do we have for salmonella typhi?

Live attenuated
What bacteria can cause paratyphoid fever
- Salmonella enterica?subsp.?Enterica
- * Salmonella enteritidis
- * Salmonella Typhimurium
- * Salmonella infantis
- * Salmonella Hadar
- * Salmonella Heidelberg
- * Salmonella paratyphi
- * Salmonella Typhi
how do we get salmonella enteritidis infection?

uncooked chicken
what is the main reservoir of salmonella enteritidis?

chickens
what does salmonella enteritidis cause

inflammatory diarrhea
what is type 3 secretion system

protein that detects eukaryotic cells and secretes protein that helps with infectivity
which bacteria have type 3 secretion system
- salmonella enteritidis
- shigella
- Yersinia pestis
What virulence factors does salmonella enteritidis have
- Capsule
- Motile
- Facultative intracellular (macrophages)
- Type 3 secretion system
What gram stain is shigella

Gram ? rod (Enterobacteriaceae)
What do shigella infections cause

Gastroenteritis with blood diarrhea
What is the clinical presentation of shigella gastroenteritis?

Bloody diarrhea
What species are in the shigella genus
- Shigella sonnei
- Shigella dysenteriae
How does shigella look when cultured on hektoin agar?

Green colonies
How do you differentiate shigella from salmonella?
- Green colonies on hektoin agar (shigella)
- Black colonies on hektoin agar (salmonella)
- Immotile (shigella)
- Motile (salmonella)
- Acid stabile (shigella)
- Acid labile (salmonella)
Which Enterobacteriaceae requires very low dose to cause infection

Shigella (10-100 organisms to cause infection)
Why are only small doses of shigella needed to cause infection

Acid stabile
How do shigella infections progress

Ingested --> intestinal lumen --> M cells --> lymphoid tissue + enterocytes
What cells are found in peyers patches

M cells
What is the function of M cells?

Sample things in the lumen and bring back antigens to the immune cells on other side of intestinal lumen
How does shigella get out of the intestinal lumen?
- Induces M cells to phagocytose them
- Escape from phagolysosome before they get degraded
- Use M cell?s actin to make a tail that it uses to propel itself from one cell to another
How does shigella move from one cell to another?

Use host cells actin cytoskeleton to create a tail that it can use to propel itself from one cell to another
What is a similarity between shigella and listeria?
- Actin rockets (listeria)
- Use actin tails created from M cell actin to propel itself (shigella)
What are virulence factors of shigella?
- Facultative intracellular
- Shiga toxin (salmonella dysinteriae)
- Type 3 secretion system
Which enterobactericiae are facultative intracellular
- Shigella
- Salmonella
What does shigella do once it has invaded lymphoid tissue + enterocytes surrounding M cells

Damages tissues + releases cytokines --> large immune response
What triggers the large immune response in shigella infection?

Release of cytokines
What does the large immune response in shigella infections cause?
- Inflammatory diarrhea
- Fecal blood and leukocytes
What can shigella dysinteriae cause
- Gastroenteritis with blood diarrhea
- Hemolytic Uremic Syndrome (HUS)
What is hemolytic uremic syndrome
- Hemolytic uremic syndrome
- Presents as acute renal failure
What causes hemolytic uremic syndrome
- E.coli (more common)
- Shigella dysinteriae
What causes Hemolytic uremic syndrome

Shiga toxin
How does shiga toxin cause hemolytic uremic syndrome
- Once in the blood stream it can induce endothelial damage including in the endothelium of the kidney --> activates platelets --> aggregation of platelets --> drop in platelet count
- Platelet clots lyse red blood cells as they pass by
What is a schistocytes

Helmet shaped red blood cell caused by hemolysis as red blood cells pass through platelet aggregates
Who is affected by hemolytic uremic syndrome

Patients under 10 years of age (shigella)
How does shiga toxin cause tissue damage

Binds to 60S subunit of ribosomes --> inhibits translation
What does shigella use type 3 secretion system for

Secrete inflammatory cytokines
What species are in the yersiniae genus
- Yersinia enterocolitica
- Yersinia pestis
Who discovered Yersinia pestis

Alexander yersin ? Swiss French
What is the cause of the black plague?

Yersinia pestis
What gram stain are yersiniae
- Gram ? rod (enterobactericiae)
- Bipolar staining
How is Yersinia enterocolitica transmitted
- Primarily through dog feces
- Contaminated milk products
Who is commonly affected by Yersinia enterocolitica

Children
Which bacteria contaminate milk
- Listeria
- Yersinia enterocolitica
Why are Yersinia enterocolitica and listeria able to infect milk

Resistant to cold temperatures
What is bipolar staining
- Stains more heavily on ends and lighter in middle
- Looks like a safety pin
Which bacteria has bipolar staining
- Yersinia enterocolitica
- Pasteurella multocida
What virulence factors does Yersinia have

Capsule
What does Yersinia enterocolitica infection cause
- Diarrhea
- Invasive --> bloody diarrhea + systemic effects
What is the clinical presentation of systemic Yersinia enterocolitica?
- Fever
- leukocytosis
- abscesses
- intestinal perforation
- intussusception
- paralytic ilius
- many other GI tract effects
- can mimic appendicitis
what kind of pain can Yersinia enterocolitica cause when in abdomen?
- mimic appendicitis
- right lower quadrant pain
what causes the black death / bubonic plague?

Yersinia pestis
what does Yersinia pestis infection cause

bubonic plague / black death
when did the black death pandemic occur

14th century
What is the main reservoir of Yersinia pestis?
- Rodents (e.g. rats)
- Prairie dogs
How is Yersinia pestis transmitted

Fleas bite the rodents and then bite the human
What is the clinical presentation of bubonic plague?
- Buboes ? swollen tender lymph nodes
- Abscesses in organs
- DIC
- Cutaneous hemorrhage
How does Yersinia pestis infection progress

Once infection established bacteria rise to higher and higher concentrations --> blood stream
What causes disseminated intracellular coagulation in Yersinia pestis infection

LPS endotoxin
What is the clinical presentation of disseminated intracellular coagulation due to Yersinia pestis?
- Necrosis of digits and other appendages
- (blackening of fingers)
What virulence factors does Yersinia pestis have
- LPS endotoxin
- Exotoxins
- Yersinia associated Outer Proteins (YOPs)
- Type 3 secretion system
What is the function Yersinia associated outer proteins
- Macrophage and neutrophil dysfunction by inhibiting phagocytosis and cytokine production
- Allows Yersinia to replicate rapidly and spread
What is the function of type 3 secretion system in Yersinia pestis?

Secrete Yersinia associated outer proteins
How do you treat Yersinia pestis infection?
- Aminoglycosides (streptomycin) + tetracycline
- Vaccine
What kind of vaccine is Yersinia pestis vaccine?

Killed vaccine
What species are in the vibrio genus
- Vibrio cholera
- Vibrio parahaemolyticus
- Vibrio vulnificus
Where is cholera endemic

Developing countries
What is the gram stain of vibrio?
- Gram ? curved rod (enterobactericiae)
- Coma shaped
What shape are vibrio

Coma shaped
What does vibrio cholera infection cause?

Cholera ? perfuse watery diarrhea (10-20L a day)
What is the clinical presentation of cholera?
- Perfuse (10-20L/day) watery diarrhea
- Rice water stool
How is vibrio cholerae transmitted

Fecal oral root by poor sanitation --> contamination of food and water sources by human feces
What is the pathogenesis of cholera?

Cholera toxin secreted by vibrio cholerae
What are the virulence factors of vibrio cholerae?
- Fimbriae
- Cholera toxin
What is the function of fimbriae in vibrio cholerae infection?

Attach the ganglioside receptors in intestinal wall
How does cholera toxin work?
- Binds to and constitutively activates adenylate cyclase of the GS pathway
- Increases cAMP
- Secretion of water into intestinal lumen
How do we treat vibrio cholerae infection?
- Oral rehydration therapy with electrolytes
- Antibiotics ? reduce duration of symptoms
How do we grow vibrio cholerae?

Alkaline media
Why is it difficult for vibrio cholerae to survive in the stomach?

Acid labile
What biochemical properties does vibrio cholerae have?
- Oxidase +
- Acid labile
Where can we find vibrio parahemolyticus and vibrio vulnificus

Contaminate sea food
What gram stain is campylobacter
- Gram ? curved rod (enterobactericiae)
- Coma shaped
What does campylobacter jejuni cause

Enterocolitis and diarrhea
How do we culture campylobacter?

Thermophilic ? likes warmth (42oC)
What is the main reservoir of campylobacter jejuni?

Intestinal tract of other animals (e.g. poultry)
How is campylobacter jejuni transmitted
- Fecal oral transmission
- During slaughtering process gut is perforated and intestinal contents can leak out and infect the meat
What does campylobacter jejuni infection causes
- A lot of watery diarrhea
- Invasive ? bloody diarrhea + bacteremia
- Reiter?s syndrome ? reactive arthritis
What shape is campylobacter jejuni

Coma shaped
What biochemical properties does campylobacter jejuni have?

Oxidase positive
Which bacteria are curved gram ? rods
- Campylobacter jejuni
- Helicobacter
- Vibrio
What is a common feature for all curved gram ? rods

Oxidase positive
How does campylobacter jejuni disease progress

Enters gut --> penetrates mucosa --> enters the blood stream
What is Reiter?s syndrome
- Reactive arthritis
- Seronegative spondyloarthropathies that can be precipitated by campylobacter jejuni infection
What can cause Reiter?s syndrome

Campylobacter jejuni infection
What is the most classic causes guillain-barr? syndrome?

Complications of Campylobacter jejuni infection
How does guillain-barr? syndrome occur

Body has autoimmune response that causes demyelination of peripheral nerves
What is the clinical presentation of guillain-barr? syndrome?

Ascending paralysis
What is the clinical presentation of botulism?

Descending paralysis
What is the difference between guillain-barr? syndrome and botulism?
- Ascending paralysis (guillain-barr? syndrome)
- Descending paralysis (botulism)
What does the name helicobacter pylori tell us?
- Helicon ? helical shape
- Pylori ? infects pylorus in the antrum of our stomach
What gram stain is helicobacter pylori

Gram ? curved rod (enterobactericiae)
What shape does helicobacter pylori have

Helical shape
Who is affected by helicobacter pylori
- 80% adults in developing countries
- 50% adults in USA
What virulence factors does helicobacter pylori have

Flagella ? motile
What does helicobacter pylori use its flagella for

Spins and whips flagella around to propel it around the stomach
What kind of motility does helicobacter pylori have?

Spinning
What biochemical properties does helicobacter pylori have?
- Urease +
- Oxidase +
What is the function of urease?
- Splits urea into ammonia and CO2
- helps reduce the acidity of the environment
why does helicobacter pylori need to invade the stomach and why

urease ? to negate the acidity of the stomach
how do we screen for helicobacter pylori infection?
- urea breath test
- biopsy during endoscopy
how do we perform the urea breath test?
- patient swallow urea labelled with radioactive carbon
- this is split into CO2 and ammonia
- CO2 labelled with radioactive carbon is exhaled
- Detect radioisotopes on exhalation
What do we detect in urea breath test?

CO2 labelled with radioisotopes
How do we detect helicobacter pylori using biopsy?

Directly check for urease with rapid test
What does helicobacter pylori infection cause

Ulcers
What is the most common cause of duodenal ulcers?

Helicobacter pylori
How does helicobacter pylori cause ulcers

Chronic infections --> reducing somatostatin / increasing gastrin production --> increased acid production
What is the risk associated with untreated duodenal ulcers?
- Adenocarcinoma of the stomach
- Lymphoma of the mucous associated lymphoid tissue (MALToma)
What bacteria is linked to almost half of gastric carcinomas

Helicobacter pylori
What is a possible treatment for MALToma?

Treatment of helicobacter pylori
How do we treat helicobacter pylori infection?
- At least triple therapy
- Proton pump inhibiter (PPI)
- Amoxicillin
- Macrolide ? clarithromycin
Why do we use a proton pump inhibiter in treatment of helicobacter pylori infections?

Counter increased acid production caused by chronic helicobacter pylori infections
What gram stain are pseudomonas

Gram ? rod (enterobactericiae)
Where do we find pseudomonas?

Aquatic environments
Why do pseudomonas cause hot tub folliculitis

Thrive in aquatic environments
What biochemical properties do pseudomonas have?
- Oxidase +
- Catalase +
What organisms are chronic granulomatous disease patients at high risk for

Catalase + organisms
Which patients are most susceptible to catalase positive organisms

Patients with Chronic Granulomatous Disease
Which bacteria are patients with CGD most susceptible to
- Chronic Granulomatous Disease ? catalase + organisms
- * SPACE, nous voyons notre chat, gros petit tresor, houra!
- * Staphylococci
- * Pseudomonas aeruginosa
- * Aspergillus fumigatus
- * Candida
- * Enterobacteriaceae
- * Neisseria
- * Vibrio
- * Nocardiae
- * Campylobacter
- * Helicobacter
- * Gardnerella vaginalis
- * Pseudomonas cepacia
- * Mycobacterium Tuberculosis
What does pseudomonas look like when plated
- Blue green pigment
- Fruity grape like odor
What produces the blue green pigment in pseudomonas?
- Pyocyanin
- Pyoverdin
Which bacteria can cause wounds to turn blue
- Pseudomonas
- Blue green pigments ? pyocyanin + pyoverdin
How do you grow pseudomonas?
- Obligate aerobe
- Thrives in aquatic environments
How do you distinguish pseudomonas from the rest of the Enterobacteriaceae family?
- Obligate aerobe (pseudomonas)
- Facultative anaerobe (others)
What can pseudomonas infection cause
- Gram ? nosocomial pneumonia
- Pulmonary infection in cystic fibrosis patients
- Osteomyelitis
- Infection of burn wounds
- Urinary Tract Infection (UTI)
- Skin lesions
- Otitis externa
What is the number one cause of gram ? nosocomial pneumonia

Pseudomonas
Who is most affected by pulmonary infections of pseudomonas
- Nosocomial pneumonia ? patients in hospital
- Pulmonary infections ? cystic fibrosis patients
What is the most common cause of respiratory failure in cystic fibrosis patients?

Pseudomonas
What is the pathogenesis of cystic fibrosis?
- Mutation in CFTR gene
- Nonfunctional transporter that regulates chloride ions
- Unable to actively pump chloride ions
Who is most affected by pseudomonal osteomyelitis
- IV drug users ? directly introduce microbe into blood stream when using needles
- Diabetics ? traumatic injury of foot due to diabetic neuropathy
What are the virulence factors of pseudomonas?
- Encapsulated
- Exotoxin A
What is a serious complication of burn injuries?

Pseudomonas
Why is pseudomonas a feared complication of burn injuries
- Often fatal
- Unresponsive to antibiotics
What is often colonized by nosocomial bacteria

Indwelling catheters
What is common clinical presentation of nosocomial pseudomonas infection

Urinary Tract Infection (UTI)
What skin lesions can pseudomonas cause
- Pruritic papular pustular folliculitis = hot tub folliculitis
- Ecthyma gangrenosum = toxin mediated cutaneous necrosis
Who is at risk of developing pseudomonal folliculitis

People using underchlorinated hot tubs
How does pseudomonas cause ecthyma gangrenosum

Exotoxin A
What does pseudomonal ecthyma gangrenosum look like

Black necrotic lesions of the skin
What is swimmers ear

Pseudomonal otitis externa ? infection of the outer ear
What do pseudomonas and Corynebacterium have in common
- Exotoxin A (pseudomonas)
- Diphtheria exotoxin (Corynebacterium diphtheriae)
How does pseudomonas exotoxin A work
- Ribosylates elongation factor 2
- Causes inhibition of protein synthesis and cell death
How do you treat pseudomonas infection?
- Antipseudomonal penicillin ? piperacillin + tazobactam
- Aminoglycosides (in combination with beta lactams)
- Fluoroquinolones ? UTI
What gram stain is Mycobacterium tuberculosis

Does not stain with gram stain
How do we visualize Mycobacterium tuberculosis?

Acid fast stain
What is acid fast stain

Carbolfuschin
Which bacteria are acid fast
- Nocordiae ? partially
- Mycobacterium
What does carbolfuschin stain in acid fast bacteria

High concentration of mycolic acids in cell wall
What are mycolic acids

Waxy fatty acids with 2 side chains
How do we grow Mycobacterium tuberculosis?
- Cultures very slowly (2-6 weeks)
- Lowenstein Jensen media
- obligate aerobe
what is Lowenstein Jensen media?
- starch + egg
- things that inhibit growth of other bacteria that may be present in patient?s sputum
how is Mycobacterium tuberculosis transmitted?

respiratory droplets
where can Mycobacterium tuberculosis grow

facultative intracellular ? in macrophages
what is the pathogenesis of Mycobacterium tuberculosis infection?
- infects someone via respiratory droplets
- fails to be cleared immediately by immune system
- primarily resides and proliferates in macrophages
what are Mycobacterium tuberculosis virulence factors?
- mycolic acids in cell wall
- chord factor = glycolipids in cell wall
- sulfatides
what is the function of the chord factor in Mycobacterium tuberculosis?

protects bacteria from being destroyed by causing granuloma formation
what is essential for virulence of Mycobacterium tuberculosis

Chord factor (glycolipids) to allow formation of serpentine like clumps of bacteria
What is chord factor of Mycobacterium tuberculosis

Glycolipids found in the cell wall that are involved in clumping of the bacteria into serpentine like formation
How does chord factor of Mycobacterium tuberculosis work?
- Increases Tissue Necrosis Factor alpha and other inflammatory cytokines
- This activates other macrophages
- Newly activated macrophages form granuloma
- Bacteria is walled off
What is the function of sulfatides in Mycobacterium tuberculosis?

Allows survival of the bacteria inside macrophages
How do sulfatides of Mycobacterium tuberculosis work
- Prevent phagolysosome fusion
- Sparing bacteria from exposure to lysosomal hydrolases
- Accumulate in phagosomes and create incompetent secondary lysosomes which are unable to fuse
How does Mycobacterium tuberculosis infection progress?
- Primary infection
- 3 different outcomes
- * Healed latent infection
- * Systemic infection = military TB
- * Reactivation of latent TB later in life
What does primary Mycobacterium tuberculosis infection cause?
- Affects lower / middle lobe of lung
- Nearby hilar lymph nodes also affected
- After primary lesion heals --> fibrotic --> calcified
What is the Ghon complex

Visible calcifications of lung parenchyma + hilar lymph nodes affected by Mycobacterium tuberculosis
How can we visualize primary Mycobacterium tuberculosis infection?

Chest x-ray to see Ghon complex
What kind of granulomas does Mycobacterium tuberculosis cause?

Caseating granuloma = tubercle
Why are granulomas formed

Attempt to wall off infection
What do granulomas look like?

Collection of activated macrophages = Langerhans giant cells
What are Langerhans giant cells

Activated macrophages found in granulomas
What do tubercles of Mycobacterium tuberculosis infection look like
- Langerhans giant cells surrounding a central area of caseating necrosis (caseating granuloma)
- Often developing fibrosis and scarring surrounding granuloma
What is the clinical presentation of Mycobacterium tuberculosis primary infection?

Prolonged fever
Who is most affected by Mycobacterium tuberculosis primary infection

Children in area endemic to tuberculosis
What is the most common path of Mycobacterium tuberculosis infection after primary infection?

Resolves heals by fibrosis and calcification and becomes latent
Who has a positive Mantoux test
- Someone after primary infection of Mycobacterium tuberculosis
- Someone with an active infection
- Someone with a latent infection
- Someone who has been vaccinated against Mycobacterium tuberculosis
What is PPD

Purified Protein Derivative (PPD)
What is the mantoux test

Tuberculin skin test using Purified Protein Derivative (PPD)
What does a positive mantoux test look like?

Wheel on skin where TB particles are injected
why is there a lump in positive mantoux test?

type 4 (delayed type) hypersentivity reaction to TB particles
what is the BCG vaccine?

developed from attenuated Mycobacterium bovis
how effective is BCG vaccine in protecting against Mycobacterium tuberculosis?

variable ranging from 0-80% effective
what happens in military TB?
- bacteremia --> Mycobacterium tuberculosis can seed in almost any organ of the body
- Acute very dangerous process that can quickly progress to death
What organs are most affected in military TB?
- Bone
- Liver
- Lymphatics
What is military TB

Systemic spread of Mycobacterium tuberculosis
What is the clinical presentation of military TB?
- Depends on the organ affected
- Fulminant multi-organ failure
- Potentially lethal
Who is most affected by military TB

Immigrant from Mycobacterium tuberculosis endemic area
Who is affected by reactivation of latent TB
- Only in 5 ? 10% people
- Associated with state of immunosuppression ? HIV / old age / cancer
How does latent TB become reactivated?

Downregulation of Tissue Necrosis Factor alpha release
What is Tissue Necrosis Factor alpha?

Pro inflammatory cytokine that causes Mycobacterium tuberculosis infection to be contained
What happens in Mycobacterium tuberculosis infection if TNF alpha is inhibited?

Immune system is defenseless --> uncontained infection
What must you do before giving a TNF inhibitor

Screen using mantoux test (PPD) to check for Mycobacterium tuberculosis latent infection
What does reactivated Mycobacterium tuberculosis infection affect most commonly
- Upper lobes of lung
- Skeletal system
- CNS
What is the clinical presentation of reactivation of TB?
- Cough
- Night sweats
- Hemoptysis = coughing up of blood
- Cachexia = wasting and weight loss
Where does reactivation of TB originate from

Within macrophages
Why do patients experience cachexia in reactivation of TB?

TNF alpha produced in reaction to chord factor promotes wasting
What is Pott?s disease
- Reactivated Mycobacterium tuberculosis infects the spinal column
- Usually multiple vertebrae are affected
What is the clinical presentation of Pott?s disease?
- Demineralization of bone with soft tissue swelling
- Pain
- Abscess formation
- Spinal deformities
- Weakness due to loss of support
How does CNS involvement of reactivated Mycobacterium tuberculosis manifest?
- Meningitis
- Tuberculoma
What is a tuberculoma

Cavitary lesion in the brain
How do we treat Mycobacterium tuberculosis?
Why does Mycobacterium tuberculosis form resistance to drugs easily?
- Treatment period is very long
- RIPE combination therapy
- * R ? Rifampin
- * I ? Isoniazid
- * P ? Pyrazinamide
- * E ? Ethambutol
- Vaccination
Why do we use combination therapy to treat Mycobacterium tuberculosis infection?

Prevent drug resistance during long course of treatment form developing
What is the treatment as prophylaxis of latent TB?

Rifampin + Isoniazid for 9 months
What gram stain is Mycobacterium tuberculosis
- Does not stain with gram stain
- Acid fast
How do we visualize mycobacterium leprae?

Acid fast stain ? carbolfuchsin
What does carbolfuchsin stain

Mycolic acid ? made of 2 waxy chains
How do we grow mycobacterium leprae?

Thrives in cold temperatures
Why does mycobacterium leprae infection affect the extremities

Prefers cooler temperatures
What is the reservoir for mycobacterium leprae?

Armadillo
What does mycobacterium leprae cause
- Leprosy = Hansen?s disease
- Tuberculoid leprosy
- Lepromatous leprosy
What is Hansen?s disease

Leprosy caused by mycobacterium leprae
What is the clinical presentation of tuberculoid leprosy caused by mycobacterium leprae?
- Relatively mild symptoms
- Well demarcated hairless hypo esthetic skin plaque anywhere on the body
What is the helper T cell immune response to tuberculoid leprosy caused by mycobacterium leprae?
- TH1 cells ? promotes cell mediated immunity
- Macrophages engulf the bacteria
What is the TH1 immune response
- Promotes cell mediated immunity
- Contains bacteria within macrophages
How do we diagnose tuberculoid leprosy caused by mycobacterium leprae?

Lepromin skin test
What is a lepromin skin test?

Intradermal injection of mycobacterium leprae antigens to test for presence of immune reaction
What is the helper T cell immune response to lepromatous leprosy caused by mycobacterium leprae?

TH2 cells ? promotes humoral response
What is the TH2 immune response

Promotes humoral response
When does lepromatous leprosy caused by mycobacterium leprae occur
- When body is unable to mount an appropriate cell mediated response
- Unable to contain the mycobacterium leprae in the macrophages
How is lepromatous leprosy caused by mycobacterium leprae transmitted?
- Unknown mode of transmission between humans
- Maybe via respiratory droplets
What is the clinical presentation of lepromatous leprosy caused by mycobacterium leprae?
- Symmetric neuropathy with glove and stocking pattern
- Numerous poorly demarcated raised lesion often on the extensor surfaces
- Profound fascial deformity ? Leonine facies
What is leonine facies
- Profound fascial deformities caused by lepromatous leprosy
- thickening of skin, loss of eyebrows and eyelashes, collapse of nose and formation of nodular ear lobes
What would you see on biopsy of lepromatous leprosy skin lesions?

Large amounts of mycobacterium leprae bacteria
What would you see on biopsy of tuberculoid skin lesions?

Small amounts of mycobacterium leprae bacteria
What is the difference between lepromatous and tuberculoid leprosy caused by mycobacterium leprae?
- 2 opposite ends of a spectrum
- Tuberculoid ? cell mediated immune response
- Lepromatous ? humoral immune response
- Tuberculoid skin lesions ? well demarcated and contain few bacteria
- Lepromatous skin lesions ? poorly demarcated and contain many bacteria
How do we treat mycobacterium leprae infection?

Long term multidrug therapy
How do we treat tuberculoid leprosy caused by mycobacterium leprae?

Dapsone + Rifampin for 6 months
Who do we treat lepromatous leprosy caused by mycobacterium leprae?
- Dapsone + Rifampin + Clofazimine for 2-5 years
- Deformities and neuropathies may not be reversible
What gram stain are actinomycetes

Gram + branching rod (filamentous)
What species are in actinomyces genus

Actinomyces Israeli
What conditions do we grow actinomyces Israeli in?

Obligate Anaerobic
Where is actinomyces found

Normal flora of the oral cavity
In what situation do actinomyces infections occur

After jaw trauma (dental procedures)
Where does actinomyces infection spread

From oral cavity --> head and neck
What infections are caused by actinomyces

Cervical facial actinomyces infection
What does cervical fascial actinomyces infection look like
- Begins with non-tender lump in jaw --> abscess --> sinus tracks that drain infection site through the skin
- Thick yellow pus
Why is pus from actinomyces infection yellow

Characteristic yellow sulfur granules
How do you treat actinomyces infection?
- Penicillin G
- Surgical drainage of complicated infections
What gram stain is Nocardiae
- Gram + filamentous branching rods
- Weak acid fast
What species are in the Nocardiae genus

Nocardiae asteroids
What conditions do we grow Nocardiae in?

Obligate aerobe
How do we tell the difference between actinomyces and nocardiae?
- Obligate anaerobe (actinomyces)
- Obligate aerobe (Nocardiae)
- Weak acid fast (Nocardiae)
what are the gram + filamentous branching rods?
- actinomyces
- nocardiae
where can nocardiae be found

in the soil
what bacteria can be found in the soil
- clostridium tetani (spore)
- clostridium perfringens (spore)
- nocardiae (gram + rod)
what is the acid fast technique of staining?

carbolfuchsin stain taken up when bacteria have mycolic acids in their cell walls
what are mycolic acids

long chained fatty acids with 2 tails
why are nocardiae weakly acid fast

contain mycolic acid in their cell walls
What biochemical markers do nocardiae have?
- Catalase +
- Urease +
Which patients are most susceptible to catalase positive organisms

Patients with Chronic Granulomatous Disease
Which bacteria are patients with CGD most susceptible to
- Chronic Granulomatous Disease ? catalase + organisms
- * SPACE, nous voyons notre chat, gros petit tresor, houra!
- * Staphylococci
- * Pseudomonas aeruginosa
- * Aspergillus fumigatus
- * Candida
- * Enterobacteriaceae
- * Neisseria
- * Vibrio
- * Nocardiae
- * Campylobacter
- * Helicobacter
- * Gardnerella vaginalis
- * Pseudomonas cepacia
- * Mycobacterium Tuberculosis
what infections does nocardiae cause
- pulmonary ? pneumonia with lung abscess formation
- CNS ? brain abscesses
- Cutaneous
Who is most affected by nocardiae infections
- Immunocompromised Men with impaired cell mediated immunity
- * HIV
- * Transplant
- * Glucocorticoids
- More common in men than women
How does pulmonary nocardiosis manifest

Pneumonia with lung abscess formation (cavitary lesions)
Where does nocardiae spread after infecting lungs
- CNS
- Can go anywhere in body
Why does nocardiae cause CNS infections

Nocardiae has affinity for neural tissue
How does CNS nocardiosis manifest

Brain abscesses
How is cutaneous nocardiosis transmitted

Open wounds exposed to dirt
How does cutaneous nocardiosis manifest

Pyogenic (inflammatory) response with production of indurated lesions
How do you treat nocardiosis?

Sulfonamides
What does clostridium tetani cause

Tetanus
What gram stain is clostridium

Gram + rod
What conditions do clostridia need to grow?

Obligate anaerobes ? cannot survive in presence of oxygen
Which bacteria are spore forming
- Clostridia genus
- Bacillus genus
Where is clostridium tetani spores often found

Soil
How can clostridium tetani cause infection
- Must get under the skin into an anaerobic environment
- e.g. under a puncture wound closed off to air
what kind of wounds are classically associated with clostridium tetani infection?
- puncture wound closed off to air
- e.g. by rusty nails or barbed wire
what are the symptoms of tetanus?
- spastic paralysis
- risus sardonicus
- lockjaw
- opisthotonus
what does spastic paralysis look like?

patients experience relentless muscle contractions leading to rigidity
what are the symptoms of botulism?

flaccid paralysis
what does risus sardonicus mean

evil smile
what is lockjaw

tense masseters prevent the jaw from opening
what is opisthotonus

characteristic extension and arching of the back due to powerful spasms of the back muscles
what is the pathogenesis of clostridium tetani?

puncture wound with foreign object with tetani spores on it --> spores are embedded in flesh --> organism vegetates and stays at wound site --> organism releases tetanus toxin --> symptoms occur
what toxins does clostridium tetani produce?

tetanospasmin
what causes the symptoms of tetanus

tetanospasmin released by the clostridium tetani
how does tetanospasmin travel in the body
- retrograde through motor axons --> spinal cord
- i.e. from the periphery --> spinal cord
how does tetanospasmin work
- acts as a protease
- cleaves SNARE proteins --> inhibits exocytosis of neurotransmitter into synapse --> neurotransmitters remain in vesicles
what kinds of neurons release gabba and glycine?
- inhibitory
- e.g. Renshaw cells
which types of neurotransmitters does tetanospasmin affect

inhibits released of gabba and glycine (inhibitory neurotransmitters) --> decreased inhibition
what do Renshaw cells do?

sense over activity of nearby motor neurons (tetanus) --> fire --> inhibit overactive neuron
what neurons are inhibited by tetanospasmin

Renshaw cells
What kind of vaccine is tetanus vaccine?

Toxoid vaccine
What is a toxoid vaccine?

Toxin conjugated to a protein to increase immunogenicity
What is the antibody response created by the tetanus vaccine?
- Antibody response to the toxin
- NOT to the organism
What does clostridium botulinum cause?

Botulism
What gram stain is clostridium botulinum

Gram + rod
Where is clostridium botulinum commonly found?
- Improper canning of foods ? flourish of bacteria
- Honey ? spores
Why is clostridium botulinum able to grow in canned foods?

Improper or insufficient heating cycles when canning food --> survival of spores --> spores germinate + flourish in anaerobic environment --> toxin is produced (heat stable)
What toxin does clostridium botulinum produce?

Relatively heat stable botulinotoxin
why is it important to cook canned food thoroughly?

denatures the relatively heat stable botulinotoxin produced in canned foods
what are the symptoms of botulism?
- descending flaccid paralysis ? absence of muscle contraction
- diplopia / ptosis of eyes in eyes
- floppy baby syndrome in babies
what is flaccid paralysis

absence of muscle contraction
How do you tell the difference between flaccid paralysis in botulism and Guillain-Barre syndrome?
- Botulism
- Descending paralysis (i.e. starts superiorly --> inferiorly)
- Affects multiple family members who have all eaten the same canned food
- Guillain-Barre syndrome
- ascending paralysis (i.e. starts inferiorly --> superiorly)
- very unusual for multiple people to present with the same symptoms
transmission of botulism in adults

bacteria grow and reproduces in anaerobic conditions of canned foods --> toxin is formed in food --> preformed toxin absorbed into the gut --> blood --> peripheral nervous system
which nervous system does botulinotoxin affect and why
- peripheral nervous system
- toxin is unable to cross the blood brain barrier
how does botulinotoxin work

protease that cleaves the SNARE protein --> prevents fusion of vesicles with presynaptic nerve terminal
what is the difference between tetanospasmin and botulinotoxin?
- tetanospasmin ? inhibitory Renshaw cells
- botulinotoxin ? motor neurons
which types of neurotransmitters does botulinotoxin affect

inhibits released of acetylcholine (excitatory neurotransmitters) --> decreased excitation
what kind of neurons release acetylcholine?

excitatory neurons
what kind of neurons are inhibited by botulinotoxin?

motor neurons
transmission of botulism in babies

honey contains many spores of clostridium botulinum which can flourish in the babies? gut
what is floppy baby syndrome

flaccid paralysis caused by botulinotoxin in newborn
what is the differences between adult and baby botulism?
- adult ? toxin is pre-formed in canned food anaerobic environment
- baby ? toxin is formed by bacteria in the gut releasing toxin in the gut
why is ingestion of clostridium botulinum spores not a risk for adults

normal gut flora outcompete it so there is no germination of spores
why is ingestion of clostridium botulinum spores dangerous to babies?
- GIT of babies is a perfect anaerobic environment
- No gut flora to compete with it
- Spores germinate + produce toxin in the gut
What is the most common form of botulism and why?
- Floppy baby syndrome
- Honey contains many spores (canned foods are less commonly infected for adults)
What gram staining is Clostridium difficile

Gram + rods
What does Clostridium difficile cause

Nosocomial diarrhea (pseudomembranous colitis)
What does nosocomial mean

People are affected while hospitalized
Why is clostridium difficile a nosocomial infection

Spores are easily transferred from patient to patient
How can you prevent passing clostridium difficile spores from patient to patient?
- Quick wipe-down with alcohol will not work
- MUST thoroughly wash with soap and water
Why Is clostridium difficile unable to infect normal individuals

Clostridium difficile is not good at competing with normal gut flora
Why is clostridium difficile able to infect hospitalized patients
- Hospitalized patients often take antibiotics which can wipe-out the normal gut flora
- This means spores are able to germinate and grow in the cleared gut
Which antibiotics are most associated with clostridium difficile infections

Clindamycin
What causes the symptoms of clostridium difficile infection

Toxin
How is clostridium difficile commonly transmitted

Improper handwashing by healthcare providers
What toxins does clostridium difficile produce?
- Exotoxin A
- Exotoxin B
What does exotoxin A do

Binds to the brush border of intestine
What does exotoxin A cause
- Inflammation
- Cell death
- Watery diarrhea
What does exotoxin B do?

Disrupts cytoskeleton integrity by depolymerizing actin
What does exotoxin B cause?
- Enterocyte death
- Necrosis
- Yellowish grey exudate --> pseudo membrane covering colonic mucosa
Why do we call Clostridium difficile infection pseudomembranous colitis?

Pseudo membrane covering the colonic mucosa is formed by exotoxin B action
How do you diagnose clostridium difficile infection?
- Visualize pseudo membrane directly either histologically or endoscopically
- Look for toxins in the stool using various assays (usually PCR)
- Do NOT look for organism
Why is detecting clostridium difficile in the stool not a good method of diagnosis for infection

Almost 1/3 patients are colonized by the bacteria without any toxins being released to cause infection
Why do we diagnose clostridium difficile using toxins?

Only toxin producing strains cause infections
How do we treat clostridium difficile infection?
- Oral vancomycin
- Metronidazole
Why do we treat clostridium difficile with oral vancomycin (and not IV)?
- Clostridium difficile bacteria are in the gut so it is better to deliver the drug to the site directly
- Vancomycin has poor absorption so there will be fewer side effects
What gram staining is clostridium perfringens

Gram + rod
In what situations do we see clostridium perfringens infections
- Motorcycle accidents
- deep penetrating wounds from military combat
- i.e. when a large amount of flesh is exposed to dirt or dust
where are clostridium perfringens spores commonly found

dirt and soil
what conditions does clostridium perfringens need to grow?

obligate anaerobe
what does clostridium perfringens cause?
- gas gangrene ? soft tissue infection (clostridial myonecrosis)
- food poisoning
what is the other name for clostridial myonecrosis and why?

Gas gangrene ? in the disease process gas is produced under the infected tissue
in what situation does clostridial myonecrosis occur

when clostridium perfringens enters a wound and causes infection
what are the clinical presentations of gas gangrene?

crepitus / crackling sound on palpation
why is gas produced in clostridial myonecrosis?

clostridium perfringens consumes carbohydrates and releases gas
what toxins does clostridium perfringens produce?

alpha toxin
what does alpha toxin cause?

necrosis
how does the alpha toxin of clostridium perfringens work?
- it is a lecithinase
- cleaves lecithin phospholipase --> damage lipoproteins --> damage of cell membranes --> hemolysis of RBC
what are the hemolytic properties of clostridium perfringens?

forms a double zone of hemolysis on blood agar
why is clostridium perfringens hemolytic?

alpha toxin
how do you differentiate clostridium perfringens from other hemolytic bacteria?

MUST be cultured anaerobically so would not grow anaerobically
How do you treat clostridium perfringens gas gangrene?

IV penicillin G
What are the symptoms of food poisoning caused by clostridium perfringens?

Late onset diarrhea
Why is clostridium perfringens diarrhea late onset?

Caused by ingestion of many spores which must germinate in the gut THEN produce toxin whilst in the gut
how does clostridium perfringens cause food poisoning?

ingestion of spores --> germination in gut --> bacteria flourish --> toxin is produced
how do you treat clostridium perfringens diarrhea?

usually transient so does not require antibiotic treatment
What Gram stain and shape are Bacilli

Gram + Rods
What species are in the Bacillus genus
- Bacillus anthracis
- Bacillus Cereus
What does a black eschar look like?

Black necrotic cutaneous lesion with surrounding erythematous ring
What does Bacillus anthracis usually look like under microscope?

Large gram + rods in chains
What is the capsule of bacilli made of?

Protein ? poly D glutamate
What conditions do bacillus anthracis need to survive?

Obligate aerobe ? only survive in the presence of oxygen
Why is bacillus anthracis able to be weaponized?

Forms spores
What does a spore allow the bacteria to do?
- hibernate in a state without any significant metabolic activity
- sturdy protective covering means it is highly resistant to temperature and chemicals
- able to survive an extremely long time in almost any external environment
- small and durable
- grow back into metabolically active state when the environmental conditions are favorable
which bacteria produce spores
- bacillus genus
- clostridium genus
what do spores do when they are in environmentally favorable conditions

revert back to a metabolically active state
what toxins does bacillus anthracis produce?
- lethal factor
- edema factor
which toxin must be present to cause symptoms in bacillus anthracis infection

both lethal factor and edema factor
how does edema factor of bacillus anthracis work?

acts as an adenylate cyclase --> increases cAMP intracellularly --> fluid goes into intracellular space --> edema
how does edema benefit the bacillus anthracis bacteria?
- inhibits host defenses
- indirectly prevents phagocytosis
how does lethal factor of bacillus anthracis work?

exotoxin that acts as a protease --> cleaves MAP kinase (signal transduction protein)
what is MAP kinase
- signal transduction protein
- involved in control of cell growth
- ultimately is responsible for tissue necrosis
what does lethal factor of bacillus anthracis cause?

tissue necrosis --> black escar
what diseases does bacillus anthracis cause?
- black escars
- pulmonary anthrax = wool sorter?s disease
where are the spores of bacillus anthracis often found and why?
- soil --> wool /hide of animals
- can survive for long periods of time
how do people get pulmonary anthrax?

inhale anthrax spores (e.g. when handling wool of sheep) --> spores germinate in lungs
what are the symptoms of pulmonary anthrax?
- starts as nonspecific pulmonary symptoms (dry cough)
- progresses to hemorrhagic mediastinitis
why is it important to catch and treat anthrax early?

bacillus anthracis can rapidly move to mediastinal lymph nodes --> hemorrhagic mediastinitis
what are the symptoms of hemorrhagic mediastinitis?
- pulmonary hemorrhage
- widened mediastinum on chest X ray
what is the mortality rate once anthrax pulmonary hemorrhage has developed?

almost 100%
how do we treat bacillus anthracis?
- drug of choice: fluoroquinolones
- secondary treatment: doxycycline
what conditions does bacillus cereus need to grow?

aerobic
what diseases does bacillus cereus cause?

food poisoning
how do we get bacillus cereus food poisoning?

eating reheated fried rice
what are the symptoms of bacillus cereus food poisoning?

vomiting and maybe diarrhea
What gram stain is Leptospira interrogans

Doesn?t stain with gram stain (spirochete)
How do we visualize Leptospira interrogans?

You can?t with a light microscope
What does Leptospira interrogans infection cause

Leptospirosis
Where is Leptospira interrogans infection endemic

Tropical regions
What is Leptospira interrogans shape
- Spirochete
- Question mark shaped
Where can we find Leptospira interrogans

Rodents / dogs
How is Leptospira interrogans transmitted
- Excreted in animal?s urine
- Transmitted to humans when they swim in contaminated water
Who is most affected by Leptospira interrogans infection

People who take part in water sports
What is the clinical presentation of Leptospira interrogans infection?
- Flu like symptoms ? fever + intense headaches
- Conjunctival suffusion ? diffuse reddening of the eyes with no inflammatory exudate
- Weil?s disease ? renal dysfunction and jaundice
What is the difference between conjunctivitis and conjunctival suffusion?

No inflammatory exudate in conjunctival suffusion
What is Weil?s disease
- Caused by Leptospira interrogans
- Renal dysfunction
- Jaundice from liver damage
What is the pathogenesis of Leptospira interrogans infection?
- Travels through bloodstream
- Multiplies in various organs ? kidneys / liver
Which organs does Leptospira interrogans affect most commonly
- Kidney
- Liver
How do we test for renal dysfunction?
- High creatinine levels
- Azotemia
What gram stain is Treponema pallidum

Doesn?t stain with gram stain (spirochete)
How do we visualize Treponema pallidum?

Can?t be visualized using light microscopy
What does Treponema pallidum cause?

Syphilis (STD)
How is Treponema pallidum transmitted?

Sexually transmitted disease
What causes syphilis

Treponema pallidum
Why is syphilis called ?the great imitatorjQuery110104336385577609254_1485168348375

Many of the symptoms look like many other diseases
What are the most common sexually transmitted diseases?
- Chlamydia (Chlamydia trachomatis)
- Gonorrhea (Neisseria Gonorrheae)
How is Treponema pallidum visualized?

Dark field microscopy
How do we collect a sample for Treponema pallidum visualization?

Direct sample from a lesion on a patient
Why is direct visualization of Treponema pallidum not commonly used?

Dark field microscopy is time consuming and not all labs are equipped to use it
How do we diagnose syphilis caused by Treponema pallidum?
- Dark field microscopy
- Blood tests
- * VDRL ? screening
- * RPR ? screening
- * FTA-Ab ? confirmatory
What is the mean screening test for Treponema pallidum?
- Venereal Disease Research Laboratory (VDRL)
- Rapid Plasmin Reagent Test (RPR)
What is the VDRL
- Venereal Disease Research Laboratory
- Non Treponema test (for syphilis)
- Tests for antibody reactivity in patient?s serum to a cardiolipin cholesterol lecithin antigen
What does VDRL test for

Antibody reactivity to cardiolipin cholesterol lecithin
Who do we screen for syphilis?
- Patients with symptoms
- Patients at high risk
Why do we get false positives in VDRL and RPR?
- Cross reactivity with other antigens
- * Mononucleosis (Epstein Barr Virus)
- * Rheumatoid factor (autoimmune)
- * Systemic Lupus Erythematosis (autoimmune)
- * Leprosy (Mycobacterium leprae)
- * IV drug users
What is the confirmation test for Treponema pallidum infection?
- FTA Antibody test (FTA-Ab)
- Treponemal test
- Tests for antibodies directly against Treponema pallidum
What does FTA-Ab test for

Tests for antibodies directly against Treponema pallidum
When do we perform FTA-Ab test?

Used after non-treponemal tests show reactivity
What are the stages of syphilis caused by Treponema pallidum?
- Early stage ? first year
- * Primary
- * Secondary
- * Early latent
- Late stage
- * Tertiary
- * Late latent
What is the clinical presentation of primary syphilis caused by Treponema pallidum?

Painless genital chancre that appears a few weeks after inoculation and heals in 3-6 weeks
How does Treponema pallidum cause genital chancres?
- Locally invading small blood vessels and damaging them
- Causes small areas of ischemic necrosis --> chancre
- Also ischemic nerve damage
When does syphilis progress to the secondary stage

When chancre is left untreated (because it is painless)
What is the clinical presentation of secondary syphilis caused by Treponema pallidum?
- Systemic disease
- Maculopapular rash everywhere including palms of hands and soles of feet that occurs weeks to months after infection
- Condyloma lata
Which STD causes rash to appear on the hands and soles of feet

Syphilis ? Treponema pallidum
What causes condyloma lata and what does it look like
- Treponema pallidum
- Flat topped bumps on mucous membranes
What causes condyloma acuminata and what does it look like
- Human Papilloma Virus
- Wart like
How can you visualize the pathogen in condyloma lata?

Dark field microscopy to see spirochete Treponema pallidum
What is the clinical presentation of tertiary syphilis caused by Treponema pallidum?
- Gomas = soft growths with firm necrotic center
- Aortitis (of ascending thoracic aorta) --> ascending thoracic aneurysm
- Tabes dorsalis = demyelination of nerves in posterior column
- argyll robertson pupil = accommodate but do not react to light
What are gomas and what causes them
- Treponema pallidum in tertiary syphilis
- Soft growths with firm necrotic center that can occur anywhere
What are the complications of aortitis caused by tertiary syphilis?
- Aneurysm
- Aorta demonstrates tree barking (thick + wrinkled)
How does syphilis cause aortic aneurysm?
- Targets vasa vasorum which supply wall of aorta --> weakening of aortic wall --> aneurysm formation
- Similar to small vessel damage --> chancre in primary syphilis
What is tabes dorsalis and what causes it
- Treponema pallidum in tertiary syphilis
- Demyelination of nerves in the dorsal / posterior columns of the spinal cord
What is the clinical presentation of tabes dorsalis in tertiary syphilis?
- Loss of vibration sense
- Propriosense --> off gait
- Discriminative touch
- lancinating pain ? piercing / stabbing pain
what is argyll robertson pupil and what causes it
- Treponema pallidum in tertiary syphilis
- Accommodate but do not react to light
Why is congenital syphilis not as common nowadays?

Standard screening of pregnant women
What is the clinical presentation of congenital syphilis?
- Constellation of symptoms in children
- Saber shins = anterior bowing of tibia
- Saddle shaped nose
What are saber shins and what infection can cause them?
- Congenital syphilis
- Anterior bowing of the tibia
- Hutchinson?s teeth ? notched incisors
- Mulberry molars ? molars with several enamel outgrowths
- Congenital deafness
How do we treat syphilis caused by Treponema pallidum?
- Penicillin in every stage and in everyone
- Should desensitize allergic patients and still use penicillin
Why can?t we use tetracycline in pregnancy?

Affects teeth and bond growth
What is the Jarisch Herxheimer reaction

Fever / chills / headache that occurs within hours of starting penicillin treatment against Treponema pallidum in syphilis
What causes the Jarisch Herxheimer reaction
- Treatment of patient with syphilis using penicillin causes huge spirochete death
- Dyeing spirochetes release a bunch of Lipopolysaccharide --> increase in cytokines
What is a good indicator that penicillin treatment is working in syphilis?

Fever / chills / headache of Jarisch Herxheimer reaction
What gram stain is Legionella pneumophila
- Gram ? thin pleomorphic
- Does not take up gram stain very well
How do we visuals Legionella pneumophila

Silver stain
How do we grow Legionella pneumophila?
- Buffered charcoal yeast extract
- In the presence of cysteine and iron
What does Legionella pneumophila infection cause
- Legionnaire?s disease ? very serious + potentially fatal
- Pontiac fever ? less serious
What is the clinical presentation of Pontiac fever caused by Legionella pneumophila?
- Fever
- Malaise
- Self-limited
Who is most affected by legionnaire?s disease caused by Legionella pneumophila

Smokers
What bacteria cause atypical pneumonia
- Legionella pneumophila
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
What does atypical pneumonia caused by Legionella pneumophila look like on chest X-ray
- Patchy infiltrate with consolidation of one lobe
- Highly variable and can easily be mistaken for another type of pneumonia
What is the clinical presentation of legionnaire?s diseases caused by Legionella pneumophila?
- Atypical pneumonia
- Hyponatremia (<130mmol/L)
- Neurologic symptoms ? headache with confusion
- Diarrhea
- High fever (>40oC)
Which bacteria causes pneumonia with diarrhea and hyponatremia

Legionella pneumophila
How do we diagnose legionnaire?s disease caused by Legionella pneumophila?
- Culture respiratory sputum ? 3-5 days
- Rapid urine antigen test
How do we treat legionnaire?s disease caused by Legionella pneumophila?
- Macrolides
- Fluoroquinolones ? have fewer complications than macrolides
How do we treat atypical pneumonia?

Macrolides
How do we treat Pontiac diseases caused by Legionella pneumophila?

We don?t ? it is self-limited
What biochemical properties does Legionella pneumophila have?

Oxidase +
What gram stain are Borreliae

Don?t gram stain (spirochete)
What are spirochetes

Bacteria that are spiral shaped
Which bacteria are spirochetes
- Borrelia
- Leptospira
- Treponema
What does Borrelia burgdorferi cause

Lyme disease
Where do we commonly find Borrelia burgdorferi

Northeastern united states
Who is affected by Borrelia burgdorferi
- People who were on hiking or camping trips
- Hunters
How is Borrelia burgdorferi transmitted
- Tick born disease
- ixodes scapularis tick
what diseases does the ixodes scapularis tick transmit?
- Lyme disease (Borrelia burgdorferi)
- Ehrlichiosis (ehrlichiae genus / Anaplasma genus)
- Babesiosis (Protozoa Babesia)
Where can we find Ixodes scapularis larvae

White footed mouse
Where can we find adult Ixodes scapularis

White tailed deer
What is the main reservoir for Ixodes scapularis?

White footed mouse
What is an obligatory host for Ixodes scapularis?

White tailed deer
What is the vector for Borrelia burgdorferi infection?

Ixodes scapularis tick
What are humans in the life cycle of the Ixodes scapularis tick

Incidental dead end host
Why don?t spirochetes gram stain

Have very thin walls
How do we visualize Borrelia burgdorferi?
- Wright stain
- Giemsa stain
Which spirochete are we able to visualize under light microscope

Borrelia burgdorferi
What is the clinical presentation of Borrelia burgdorferi infection?
- 3 stages
- 1. Erythema chronica migrans
- 2. Heart block caused by myocarditis + bilateral fascial nerve palsy
- 3. Migratory polyarthritis + Encephalopathic effects
What does erythema chronica migrans in Borrelia burgdorferi infection look like
- Bulls eye rash
- Not painful
- Not puritis
- Flu like symptoms
What is the name for the bull?s eye rash you get in Borrelia burgdorferi infection?

Erythema chronica migrans
When do we see erythema chronica migrans?

One month after tick bite infected with Borrelia burgdorferi
What is bell?s palsy

Idiopathic fascial nerve palsy
What is the second stage of Borrelia burgdorferi infection?
- Heart block caused by myocarditis
- Bilateral fascial nerve palsy
What is the clinical presentation of migratory polyarthritis caused by Borrelia burgdorferi infection?
- Arthritis of large joints (e.g. knee)
- Many joints can be affected
- Can move from joint to joint
What are the CNS effects of Borrelia burgdorferi infection?
- Subtle Encephalopathy
- Memory difficulty
- Cognitive slowing
- Lymphocytic meningitis
How do we treat Borrelia burgdorferi infection?
- As early as possible
- Doxycycline ? in stage 1
- Ceftriaxone ? later presentation
Which species are in the Rickettsiae genus
- Rickettsia prowazekii
- Rickettsia rickettsii
Where can Rickettsiae grow

Obligate intracellular ? unable to produce NAD+ and CoA
What gram stain are Rickettsiae
- Does not take up gram stain very well
- Gram ? coccobacillus
How do we visualize Rickettsia?

Giemsa stain
Why are Rickettsiae obligate intracellular
- Unable to produce NAD+ and CoA
- Both are needed for bacterial growth and replication
- Get them form eukaryotic cells instead
What is the Weil Felix test?
- Agglutination test to diagnose Rickettsial infections
- Tests for cross reactivity between Rickettsia species and Proteus Vulgaris
- Not very sensitive or specific
What are the general prodromal symptoms of a Rickettsial infection?
- Headache
- Fever
- Vasculitis
Which vessels are affected by vasculitis in Rickettsial infection
Thin blood vessels of capillary beds
- What is the clinical presentation of vasculitis caused by Rickettsial infections?
- Granular bumpy rash
How do we treat Rickettsiae infections?

Tetracycline ? doxycycline
What is the clinical presentation of epidemic typhus caused by Rickettsia prowazekii?
- Rash that starts at trunk and spreads to extremities
- Rash spares hands, feet and head
- Myalgia + arthralgia
- Pneumonia
- Encephalitis with dizziness and confusion
- Coma
Who is most affected by Rickettsia prowazekii
- Anyone living in close quarters (e.g. military or prisoners)
- Poor hygiene
How is Rickettsia prowazekii transmitted

Arthropod vectors ? lice
Why are lice a good vector for spreading of Rickettsia prowazekii
- Feed on human blood
- Defecates near feeding site
- Scratching --> introduction of bacteria into blood stream
What does Rickettsia prowazekii infection cause

Epidemic typhus
What is the difference between Rickettsia prowazekii and Rickettsia typhi?
- Epidemic typhus (prowazekii)
- Endemic typhus (typhi)
What does endemic mean

disease localized to a region that doesn?t necessarily comment on magnitude of population getting illness
what does epidemic mean

wide spread rampant outbreak
what does Rickettsia rickettsii cause

rocky mountain spotted fever
how is Rickettsia rickettsii transmitted

arthropod vectors ? dermacentor tick
how do dermacentor ticks transmit Rickettsia rickettsii infection

direct biting
what is the clinical presentation of rocky mountain spotted fever caused by Rickettsia rickettsii?
- incubation period ranging from 2-14 days
- rash starts at ankles and wrists --> central
- rash covers hands and feet in later stages of disease
- headache
- fever
- myalgia ? sever muscle pain
What does Coxiella burnetii infection cause

Q fever
What gram stain is Coxiella

Gram ? coccobacillus
What is the clinical presentation of Q fever caused by Coxiella burnetii?

No rash
Where can we fine Coxiella burnetii

Obligate intracellular
How is Coxiella burnetii able to survive digestive tracts of animals

Forms a sturdy spore like structure
Where can we find Coxiella burnetii ?spores?

In animal droppings in dirt
How is Coxiella burnetii transmitted

Aerosol transmission
What is a major reservoir for Coxiella burnetii?

Farm animals
Who is most affected by Coxiella burnetii
- Farmers
- Veterinarian that has just delivered a baby animal and was exposed to placental excretions
What is the clinical presentation of Q fever caused by Coxiella burnetii?
- Pneumonia
- Headache
- Fever
- Hepatitis
How do you tell the difference between Q fever (Coxiella burnetii) and Brucellosis?
- Brucellosis ? undulating fever
- Both have pneumonia and hepatitis symptoms
How do you treat Q fever caused by Coxiella burnetii?
- Usually self-limiting ? goes away within 2 weeks
- Pasteurizing milk kills most organisms
- Vaccine
Who can get chronic Q fever caused by Coxiella burnetii
- Immunocompromised patients
- Patients with previous valvular damage
What is the clinical presentation of chronic Q fever caused by Coxiella burnetii?

Endocarditis
What kind of vaccine is Coxiella burnetii vaccine?

Acellular
Who gets the Coxiella burnetii vaccine
- Veterinarians
- Other high risk people ? farmers
What species are in the Bartonella genus

Bartonella henselae
What does Bartonella henselae cause
- Cat scratch fever
- Bacillary angiomatsosis
What gram stain are Bartonella

Gram ? rod
How do we visualize Bartonella henselae?

Warthin starry stain ? type of silver stain
What is the Warthin starry stain?

Type of silver stain used to stain Bartonella henselae
What is the clinical presentation of cat scratch disease caused by Bartonella henselae?
- Fever
- Painful large lymph nodes in axilla ? lymphadenitis
How is Bartonella henselae transmitted

Cat scratches or bites
Who is affected by cat scratch disease caused by Bartonella henselae

Immunocompetent healthy people
Who is affected by bacillary angiomatosis caused by Bartonella henselae
- Immunocompromised people
- HIV infected patients
What is the clinical presentation of bacillary angiomatosis caused by Bartonella henselae?
- Fever chills headaches
- Raised red vascular legions all over skin
What is similar between Kaposi sarcoma and bacillary angiomatosis
- Immunocompromised patients ? HIV
- Red vascular lesions on skin
How do you differentiate between Kaposi sarcoma and bacillary angiomatosis caused by Bartonella henselae?

Skin biopsy stained with Warthin starry silver stain
How do you treat bacillary angiomatosis caused by Bartonella henselae?
- Doxycycline
- Macrolides ? azithromycin
How do you treat cat scratch disease caused by Bartonella henselae?
- Usually self-limited so don?t treat
- Azithromycin ? if swelling and pain from lymph nodes too severe
What species are in the chlamydia genus
- Chlamydia trachomatis
- Chlamydophila pneumoniae
- Chlamydophila psittaci
How is chlamydia transmitted

Sexually transmitted disease
Where can chlamydia grow

Obligate intracellular bacteria
What gram stain are chlamydia

No staining with gram stain
What do chlamydiae and rickettsia have in common
- Both obligate intracellular organisms ? can?t create their own ATP
- Both stain poorly with gram stain
Why are chlamydia obligate intracellular organisms?

Cant create own ATP
What is special about chlamydia cell wall

Does not have muramic acid
What is muramic acid

Part of peptidoglycans that make up the cell wall
What is the life cycle of chlamydia?
- Elementary bodies
- Reticular bodies
What is the elementary body of chlamydia?
- 1st stage of life cycle
- Found outside of cell
What is the reticular body of chlamydia?
- 2nd stage of life cycle
- Found inside the cell
Where and how do chlamydia multiply
- Inside cells
- By binary fission
Which form of chlamydia is the active form
- Reticular body
- Able to multiply
How are newly formed chlamydia released from cells

In their elementary form
Which form of chlamydia is the infectious form

Elementary body
How do we visualize chlamydia?
- Giemsa stain
- See inclusion bodies in cells infected with chlamydia under the microscope
What are chlamydia inclusion bodies?
- Bunches of reticular cells dividing inside the cell
- What do we use Giemsa stain to visualize?
- Chlamydia
- Borrelia
How do we diagnose chlamydia infection?

Nucleic Acid Amplification test (NAAT)
What is NAAT
- Nucleic Acid Amplification Test
- Basically PCR
What serovars are there in chlamydia trachomatis species
- A-C
- D-K ? STD
- L1-L3
what is the most common bacterial STD in USA?

chlamydia trachomatis D-K infection
what does chlamydia trachomatis D-K cause?

sexually transmitted disease
what is the clinical presentation of chlamydia trachomatis D-K infection?
- symptoms vary / remain asymptomatic
- watery discharge
- can progress ? Pelvic inflammatory disease
what is the difference between chlamydia and gonorrhea?
- Chlamydia ? watery discharge (chlamydia trachomatis D-K)
- Gonorrhea ? mucopurulent white discharge (Neisseria gonorrhea)
- Chlamydia ? congenital conjunctivitis after 1st week of life
- Gonorrhea ? congenital conjunctivitis within first 2-4 days of life
What is pelvic inflammatory disease

Ascending infection that can lead to cervicitis, salpingitis, pelvic pain, abscess formation, scarring of the tubes that can lead to infertility / atopic pregnancies later in life
Why is it important to treat STDs as soon as possible ]

To avoid progression to pelvic inflammatory disease and its complications (including infertility / atopic pregnancies)
What do congenital chlamydia trachomatis D-K infection cause
- Neonatal conjunctivitis
- Neonatal pneumonia
How does congenital chlamydia D-K occur

When mother gives birth whilst with an active infection
What is the clinical presentation of chlamydia trachomatis D-K congenital conjunctivitis

Conjunctivitis occurs after first week of life
What is the clinical presentation of chlamydia trachomatis D-K pneumonia

Staccato cough ? cough with short sudden bursts
What is the most common serovar to cause chlamydia STD?

D-K
What do chlamydia trachomatis L1-L3 cause?

Lympho Granuloma Venereum (LGV)
What is LGV caused by chlamydia trachomatis L1-L3
- Lymphogranuloma venereum
- Infection of the inguinal lymph nodes
What is the clinical presentation of chlamydia trachomatis L1-L3 lymphogranuloma venereum?
- Starts as painless genital ulcer (like syphilis)
- Tender lymphadenopathy with draining lymph nodes weeks-months later
What do chlamydia trachomatis A-C cause?

Trachoma
What is the leading cause of blindness in the world?

Trachoma caused by chlamydia trachomatis serovars A-C
How are chlamydia trachomatis A-C transmitted?
- Hand to eye contact
- Fomites
What are long term complications of chlamydia trachomatis infection
- Pelvic Inflammatory disease in women --> infertility / atopic pregnancies
- Reactive arthritis = Reiter?s syndrome
What is the pathogenesis of Reiter?s syndrome?
- Maladaptive autoimmune response
- Antibodies against bacteria cross react and attack the body
What is the clinical presentation of Reiter?s syndrome?
- Can?t see, can?t pee, can?t climb a tree
- Reactive arthritis often in sacro-iliac joint / knee
- Uveitis = infection of the eyes
- Urethritis
What could cause Reiter?s syndrome
- Campylobacter
- Chlamydia
How do we treat chlamydia infection?
- Treatment is very effective
- Macrolides ? azithromycin
- Tetracycline ? Doxycycline
Why can?t we use penicillins to treat chlamydia infections?

Do muramic acid in their cell wall so antibiotics that target cell wall?s cannot be used
How do we treat neonatal conjunctivitis caused by chlamydia trachomatis D-K?
- Topical macrolides are not effective for conjunctivitis in the newborn
- Oral Macrolides must be given
Why do we use combination therapy to treat chlamydia trachomatis D-K STD?
- Treat for gonorrhea too
- Often have a coinfection with Neisseria gonorrhea
- Often hard to tell them apart as they present almost identically
How do we treat chlamydia trachomatis D-K STD?
- Combination therapy
- Macrolides ? azithromycin (chlamydia trachomatis D-K)
- Ceftriaxone (Neisseria gonorrhea)
What does chlamydophila pneumoniae infection cause

Atypical pneumonia in adults
What is walking pneumonia

Atypical pneumonia
What bacteria cause atypical pneumonia
- Legionella pneumophila
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
Which bacteria more commonly causes atypical pneumonia in the elderly

Chlamydophila pneumoniae
How do we treat chlamydophila pneumoniae atypical pneumonia?
- Tetracycline ? doxycycline
- Macrolides ? azithromycin
What does Mycoplasma pneumoniae cause

Walking pneumonia = atypical pneumonia
What gram stain is mycoplasma

No gram stain
Why doesn?t mycoplasma stain with gram stain

No cell wall
What do mycoplasma have instead of a cell wall

Special cell membrane with cholesterol in it
What is the function of cholesterol in mycoplasma cell membrane?
- Stabilize membrane
- Allow membrane to be more flexible
What is the only bacteria with cholesterol in their cell membrane?

Mycoplasma
What is the molecular structure of a sterol?

4 ringed structure made of benzene rings
What bacteria cause atypical pneumonia
- Legionella pneumophila
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
Why do we call atypical pneumonia this way?

Can?t easily culture or isolate the microbes causing it
Why do we call atypical pneumonia caused by Mycoplasma pneumoniae a walking pneumonia?

Severe pneumonia seen on X-ray but not too many clinical symptoms
What is the clinical presentation of walking pneumonia caused by Mycoplasma pneumoniae?
- Few clinical symptoms
- X-ray appears much worse than patients do clinically
What does an X-ray for Mycoplasma pneumoniae atypical pneumonia look like?

Reticulo nodular / patchy infiltrate
Who is most affected by Mycoplasma pneumoniae infection

Young adults in areas of close contact (e.g. Military)
How do you diagnose Mycoplasma pneumoniae infection?

Cold agglutinins found in 50-70% patients
How do we grow Mycoplasma pneumoniae?
- Takes a week
- Eaton?s agar
What are cold agglutinins
- 1-2 weeks into Mycoplasma infection people develop IgM molecules that agglutinate erythrocytes in cold temperatures
- Can lead to lysis of red blood cells
What is the molecular structure of IgM?

Pentamere circles
How do we treat Mycoplasma pneumoniae infection?

Macrolides ? erythromycin
Why can?t we use penicillins to treat mycoplasma pneumoniae infection?
No cell wall so cannot use antibiotics that target cell wall
- What does Enterobacter cloacae infection cause?
- Pneumonia
- Urinary Tract Infection (UTI)
Where do we find Enterobacter cloacae?

In hospitals ? nosocomial infections
Why is Enterobacter cloacae a nosocomial infection?

Multidrug resistance
How do we treat Enterobacter cloacae infection?

Carbopenems ? no resistance
why are there nosocomial infections

multidrug resistance
how do we treat nosocomial infections?

Carbopenems ? no resistance
what are Enterobacter cloacae biochemical properties?

ferment lactose
which Enterobacteriaceae ferment lactose
- Enterobacter
- Serratia
- Klebsiella
- E. coli
How do we detect lactose fermenters?

Form pink colonies on MacConkey agar
What gram stain is Enterobacter cloacae

Gram ? rod (Enterobacteriaceae)
What are Enterobacter cloacae virulence factors?

Motile
What does serratia marcescens infection cause
- Pneumonia
- Urinary Tract Infection (UTI)
Where do we find serratia marcescens?

In hospitals ? nosocomial infections
Why is serratia marcescens a nosocomial infection

Multidrug resistance
How do we treat serratia marcescens infection?

Carbopenems ? no resistance
what are serratia marcescens biochemical properties

ferment lactose (very slowly)
what gram stain is serratia marcescens

gram ? rod (Enterobacteriaceae)
what are serratia marcescens virulence factors

motile
how do we differentiate serratia from other Enterobacteriaceae?

produces red pigment when cultured
where can you find serratia bacteria

anywhere ? e.g. pink ring when don?t clean shower is serratia
What does klebsiella pneumoniae infection cause
- Pneumonia
- Urinary Tract Infection (UTI)
Where do we find klebsiella pneumoniae?

In hospitals ? nosocomial infections
Why is klebsiella pneumoniae a nosocomial infection

Multidrug resistance
How do we treat klebsiella pneumoniae infection?

Carbopenems ? no resistance
what are klebsiella pneumoniae biochemical properties
- ferment lactose
- urease positive
what gram stain is klebsiella pneumoniae

gram ? rod (Enterobacteriaceae)
who does klebsiella pneumoniae affect

alcoholics ? due to aspiration
how do klebsiella pneumoniae pass into the lungs

aspiration
how does klebsiella pneumoniae infection present
- abscesses ? cavitary lesions that resemble TB
- current jelly sputum
what are the virulence factors of klebsiella pneumoniae?
- polysaccharide capsule
- NON motile
what is the capsule of klebsiella pneumoniae mad of?
polysaccharide
- What species are in the proteus genus
- Proteus mirabilis
What gram stain are proteus

Gram ? rod (enterobactericiae)
What does proteus look like when plated
- Demonstrates swarming motility
- Fishy odor
What are virulence factors of proteus?

Motility
What kind of motility does proteus have?

Swarming motility when plated
What shape do kidney stones formed in the renal pelvis due to proteus have?

Stag horn calculi
What do proteus infections cause
- Stag horn calculi of the renal pelvis
- Urinary Tract Infections (UTI)
What are biochemical properties of proteus

Urease +
What is important for proteus to be able to form stag horn calculi

Urease
What is the function of urease?
- Produces ammonia and CO2 rom urea
- Creates alkaline environment
How does proteus cause stag horn calculi
- Creates alkaline environment (urease)
- Perfect environment for precipitation of struvite stones
What are struvite stones made of?
- Ammonia
- Magnesium
- Phosphate
What is the complication of struvite kidney stones?
- Pain
- Kidney damage
- Nidus for proteus --> recurrent infections
How do you treat proteus infection?

Sulfonamides
Who is the founding father of microbiology?

Louis Pasteur
Where can we find Pasteurella multocida

Respiratory tract of small mammals ? cats / dogs
How is Pasteurella multocida transmitted to humans

Dogs and cat bites
What does Pasteurella multocida infection cause
- Soft tissue infections --> Cellulitis in first 24 hours --> necrotizing fasciitis / osteomyelitis
- Lymphadenopathy
- Systemic infection
What is the clinical presentation of Pasteurella multocida infection?

Erythematous area of skin where bite is
How long after initial exposure does Pasteurella multocida cause infection

Within first 24 hours
Who is at most risk for systemic spread of Pasteurella multocida
- Liver disease patients
- COPD patients
What biochemical properties does Pasteurella multocida have?
- Catalase +
- Oxidase +
What are Pasteurella multocida virulence factors

Capsule
How do we grow Pasteurella multocida?

5% sheep?s blood agar
What gram stain is Pasteurella multocida
- Gram ? coccobacillus
- Bipolar staining = safety pin staining
What is bipolar staining
- Bacteria takes up stain most readily at its 2 ends
- Looks like safety pin
Which bacteria demonstrate bipolar staining
- Pasteurella multocida
- Yersinia enterocolitica
How do we treat Pasteurella multocida infection?
- Penicillin ? amoxicillin
- AND Beta lactamase inhibitor (prevent resistance) ? clavulanic acid
Why do we use combination of penicillin and beta lactamase inhibitor in treatment of Pasteurella multocida?

To prevent development of resistance
What does chlamydophila psittaci cause

Pneumonia
How is chlamydophila psittaci transmitted

Birds ? often parrots
What does Gardnerella vaginalis cause

bacterial vaginosis
what is the clinical presentation of bacterial vaginosis caused by Gardnerella vaginalis?

thin greyish white malodorous (fishy) discharge from vagina
what gram stain is Gardnerella vaginalis
- Gram variable rod
- Stains as either gram + or gram -
How does Gardnerella vaginalis cause infection
- Increase in anaerobic flora of the vagina --> overgrowth --> decreased amount of lactobacilli
- Creates environment more suitable for Gardnerella vaginalis
What is the normal vaginal flora?
- Mainly Lactobacilli
- Minority of anaerobic gram ?
How do we diagnose vaginosis caused by Gardnerella vaginalis?
- Discharge should have a pH above 4.5 (usually between 5 ? 6.5)
- Whiff test
- Microscopic exam ? with wet mount
What is the whiff test?
- Prep vaginosis discharge with 10% KOH and smell pungent fishy odor
- Diagnosis for Gardnerella vaginalis vaginosis
How do we do a microscopic exam of Gardnerella vaginalis
- Wet mount preparation of bacterial vaginosis discharge
- Clue cells
What are clue cells

Epithelial cells diffusely coated with Gardnerella vaginalis bacteria
How do we treat bacterial vaginosis caused by Gardnerella vaginalis?

Metronidazole
Which bacteria do we treat using metronidazole
- Clostridium difficile
- Gardnerella vaginalis

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Author

Marine

327614

Card Set

Flashcards Bacteria

Description

Bacteriology missing: Bordetella parapertussis other haemophilus species Corynebacterium other potentially pathogenic corynebacterium Arcanobacterium Haemolyticum Characterisation fo Enterbacteriaceae family Non typhoidal salmonella spp Other clinically non-significant non fermenters (Acinetobacter, Burkholderia, Stenotrophomonas) Atypical mycobacteria Non spore forming anaerobes Borrelia recurentis other mycoplasma

Updated

2017-01-23T10:47:34Z

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