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toxic shock syndrome toxin 1
- exotoxin, superantigen, causes staphylococcal toxic shock syndrome with systemic side effects despite isolated site growing staphylococci such as vagina of menstruating woman. Causes proliferation of large amounts of T cells, resulting in large amounts of cytokines (interlukin 1 beta and tumor necrosis factor alpha). Cytokines cause fever and shock and organ failure, vomiting, diarrhea, rash, sore throat. Blood cultures are negative to bacteria because it is toxin mediated. Desquamation of skin upon resolution. Wound infections can cause toxic shock syndrome with enterotoxins, not TSST-1
- distinguish from streptococcal toxic shock syndrome because it has rash and is associated with tampon use
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Superantigen
Binds to the side of the receptor, causing a high number of activated T cells because this way of binding has much lower specificity
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Staphylococcal enterotoxins A-E, G-I
- Superantigen
- Acts on neural receptors in the upper GI, causing vomiting 2-5 hours after injestion
- Toxins are resistant to boiling for 30 minutes
- Self limited
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Exfoliatin/Exfoliative toxin
Cause of scalded skin syndrome, disrupting the junction between the stratum spinosum and stratum granulosum, so it is not painful
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Alpha hemolysin/alpha toxin
Creates a pore to injure. Perhaps in body does not work this way, but it might lyse other cells or just form pores
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Panton-Valentine (PVL)
Associated with many community acquired methycillan restance staphylococcus aureus via a phage
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Coagulase
binds prothrombin to create a complex, which contributes to a fibrin capsule, and does not let neutrophils access
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Protein A
- Endotoxin
- Prevents antibody related clearance, binding to Fc portion of IgG
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Carbuncle and Faruncle
- Furuncle is a boil from the blockage of a sweat gland or hair follicle
- Carbuncle infection spreads from faruncle
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Septic arthritis and osteomyelitis
Distant joint and bone infections due to bacteria gaining access to the blood stream
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Endocarditis
- Heart valve infection through biofilm
- Difficult to treat and frequently leads to death
- Especially common in IV drug users
- Signs can be osler’s nodules (raised red lesions on hands and feet), janeway’s lesions (small non-tender hemorrhages on palms and soles), conjunctival petechiae, splinter hemorrhage
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Cellulitis
- Deeper than scalded skin syndrome
- Infection of skin and soft tissue
- associated with fever and lymphangitis
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Catalse test
- Add H2O2 and if bubbles (releases O2) is positive
- Negative does not bubble
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Coagulase test
- Mix with rabbit serum to see if it polymerizes fibrin
- Positive clumps, negative does not
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Streptolysin O
- SLO forms pores in plasma membranes of human cells
- does beta hemolysis
- can use ASO, antistreptococcal streptolysin O titers to diagnose
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M-protein
- Fribrillar molecules anchored to peptidoglycan (endotoxin)
- prevent phagocytosis
- used to serotype streptococcus pyogenes
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Streptococcal pyrogenic exotoxins
- aka erythogenic toins or scarlet fever toxins
- sarlet fever rash
- streptococcal toxic shock syndrome
- SPE A and SPE C are superantigens carried by phages (example of phage conversion) and contribute to hypotension and shock
- SPE B is a protease that may contribute to tissue destruction in necrotizing fasciitis
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Streptococcal pharyngitis
- very common especially in young children
- swollen lymph nodes
- headache
- sore throat
- fever
- usually self limiting
- clinically cannot differentiate from viral pharyngitis
- can be accompanied by scarlet fever
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Scarlet fever
- sand paper rash
- circumoral pallor
- can accompany streptoccal pharyngitis
- accentuated rash in skin creases
- strawberry tongue
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Streptococcal toxic shock syndrome
- Fever, hypotension, multi organ failure
- Bacteremia
- Associated soft tissue infection like impetigo or sequelae
- distinguished from staphylococcal toxic shock syndrome because no rash and no tampon use association
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Impetigo
- usually in small children with poor hygiene
- small vesicles on skin enlarge, become pustular and rupture to form yellow crust
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Erysipelas
- rash, special type of cellulitis
- endurated, erythematous, well demarcated, rapidly enlarging, usually on face
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Necrotizing fasciitis
- Deeper than cellulitis
- superficial and/or deep fascia involving muscle and life threatening
- can be from small cut or surgical wound
- very rapid production, considered a surgical emergency to remove necrotic tissue
- severe pain at site of infection
- fever, malaise, minimal physical findings
- mottled dusky skin over necrotic tissue with bullae (blisters)
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Nonsuppurative sequelae
- autoimmune disease because streptococcus pyogenes has surface antigens similar to our own tissues
- most of damage in heart valves
- onset 3 weeks after pharyngitis
- Does not follow soft tissue infections
- Jones criteria for diagnosis
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Poststreptococcal glomerulonephritis
- due to poor kidney funciton
- following pharyngitis or soft tissue infection
- edema, hypertension, hematuria and proteinuria
- usually self limited
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VanA operon
- Enterococci spp. have as part of their transposon
- transposon carried by plasmid
- synthesizes and substitutes D-ala-D-ala for D-ala-D-lactate, which vancomycin cannot bind
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A-B toxin
- 2 subunits that work together to inject the toxin into the cell
- A is activity and has an edema factor and a lethal factor EF and LF
- B is the binding subunit with protective antigen PA
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Anthrax toxin
- A-B toxin
- plasma encoded
- protective agent PA binds to cells and facilitates edema factor and lethal factor EF and LF
- EF increases cAMP through adenylate cyclase activity increase and inhibits neutrophils
- LF has zinc protease, which cleaves the kinases of the host cell leading to macrophage cell death
- we have stopped all this just by administering a small amount of mutant protective agent PA
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Cutaneous anthrax
- spores introduced to skin
- small red macula painless
- macula enlarges to form ulcer and middle can become necrotic (blackened necrotic eschar)
- surrounded by small satellite vesicles
- spontaneous resolution
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Inhalation anthrax
- spores inhaled often from contaminated hides, hair or wool
- fever, shortness of breath, hypotension, death
- widening of mediastinum due to lymphadenopathy
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Gastrointestinal anthrax
- from eating contaminated meat
- mortality rate between cutaneous and inhalation
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Diptheria toxin
- carried on phage
- A-B toxin that keeps disulfide linkage after cleavage (then full cleavage inside cell)
- fragment A inhibits peptide elongation through ADP-ribosylating EF-2
- inhibits protein synthesis in pharyngeal cells, leading to necrosis
- psuedomembrane is necrotic debris, fibrin, blood cells
- airway obstruction possible
- can be absorbed into blood stream and go elsewhere
- heart causing cardiac arrhythmias
- nerve leading to paralysis of eye muscles, soft palate, and extremities
- adrenal damage causing hypoadrenalism
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ADP-ribosylating toxins
- transfer ADP-ribose from NAD to host cell proteins
- alters protein activity
- example is inhibiting EF-2
- fragment A of diptheria toxin
- cholera toxin (Vibrio cholerae)
- heat labile Escherichia coli toxin
- pertussis toxin (Bordetella pertussis)
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Toxoid
- vaccine
- chemically treated toxin so that it is no longer toxic
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Tetanus toxin
- botulinum toxin homolog
- A-B binds to peripheral motor neurons terminals
- transported to cell body in CNS
- blocks presynaptic inhibitory neurotransmitters
- increases firing rate
- more rigidity 1st seen in masseter then neck, shoulder, back, then abdomen and leg
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Botulinum toxin
- tetaun toxin homolog
- A-B linkage with disulfide
- destroyed by boiling 10-15 minutes
- protease, some encoded by bacteriophages
- enters blood stream to cholinergic terminals at peripheral motor endplates
- cleaves neuroexocytosis apparatus blocking acetylcholine release
- decreases motor neuron activity
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Pulmonary nocardiosis
- subacute pneumonia
- nodules, cavitation, empyema (pus/infection of pleural cavity)
- dissemination to CNS, skin, soft tissues, other organs forming abscesses
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Transcutaneous inoculation
- aka actinomycetoma
- gets into cuts in foot
- fistulas with discharge of serous/purulent material with sulfur granules
- lessions slowly spread to involve skin, subcutaneous tissue and bone
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Heat labile toxin
- A-B similar to cholera
- stimulates adenylate cyclase in gut epithelial cells
- plasmid encoded
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Heat stable toin
- stimulates guanylate cyclase in gut epithelial cells
- plasmid encoded
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SPI-1 type III secretion system
- ruffles enterocytes so that bacteria can enter
- survive and multiply in phagosomes
- serovar typhi can survive in macrophages
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Type III secretion system
- directly injects bacterial proteins into the cytoplasm of the host
- toxins secreted to exterior of bacterium
- then translocation complex inserted into host cell membrane
- toxins translocated into cell
- effector proteins (toxins)
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Dysentery
- cramps
- painful straining to pass stools
- frequent small bloody mucoid stools
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Typhoid fever
- prolonged fever with persistent bacteremia
- diarrhea
- sometimes constipation
- abdominal pain
- rash of a few pink macules, rose spots, observed
- can infect gallstones leading to carrier state where for years it is shed in feces
- prevention by parenteral capsular vaccine/live attenuated oral
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Bubonic plague
- Yersinia pestis colonizes forgut of flea
- makes a biofilm so the bacteria bites more
- flea vomits and bacteria travel in blood to nearest lymph node
- 2-6 day incubation
- bubo near bite, fevers, chills, myalgias, arthralgias and headache
- bubo grows in size and pain and erythematous
- sepsis and death
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Pneumonic plague
- 1-4 day incubation
- fever, chills, myalgias, headache, weakness
- productive cough sometimes bloody and dyspnea
- high mortality rate
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Primary septicemic plague
- From direct inoculation of organism into blood stream
- Nausea, vomiting, diarrhea and abdominal pain
- Hard to diagnose early so very fatal
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Pertussis toxin
- A-B hexamer of S1-S5
- S2 S3 S4x2 adhere
- S1 ADP-ribsoylates G protein causing increased cAMP
- S5 scaffolds S1-S4
- also increases number of CR3 molecules on cell
- blocks neutrophil recruitment
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Zoonotic infection
- infection acquired directly or indirectly from animals
- indirect is like a flea or mosquito etc
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Histopathology of TB
- cellular immune response recruits macrophages, monocytes, neutrophils
- macrophages differentiate into mulinucleated giant cells, foamy macrophages and epithelioid macrophages
- lymphocytes recruited surround
- fibrous layer forms around maccrophages=granuloma
- dying macrophages make necrosis in center=caseating granuloma
- bacteria survive this, granuloma ruptures, bacteria in airway to be coughed
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Purified Protein Derivative of Tuberculin
- skin test with purified culture injected
- if immunesystem reacts its positive
- delayed 2-3 days
- can react with other mycobacterium
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Interfuron-gamma release assays
- does not react with other mycobacterium
- just send a blood or lymph sample
- lymphocytes produce interfreron-gamma detected by ELISA
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