MMI Part 3.0

A microorganism that can cause a disease process

• Always cause disease even in healthy immunocompetent individuals
• eg. Bacillus anthracis

• A microorganism that may cause disease if given the right circumstances
• e.g. Candida abicans and Mucor species - immunosuppression

• A measure of the amount to which the microorganism is pathogenic
• eg. Streptococcus pneumonia is a pathogen, but only when it produces a capsule - a virulence factor

Ability to cause disease by evading or overcoming the host defenses

• Pathogen find suitable host
• Pathogen adheres to host tissues
• Pathogen penetrates host defenses

Sometimes a pathogen can cause disease without penetrating the body by releasing toxins

• Most organisms must establish a foothold
• Adherence = the first step towards establishment of infection
• Penetration of host cell walls/membranes then occurs
• Facilitated by structures on the pathogens called adhesions or ligands and structures on the host cells that recognize and bind with these: receptors
• Most adhesions/ligands are glycoptorteins or lipoproteins
• Most receptors are sugars, eg. mannose

• N. gonorrhoeae: pii or fimbriae contain adhesins
• S. mutans: glycocalyx
• Enteropathogenic E. cole: specialized fimbriae that only bind to certain intestinal cells
• Adherence "Lock and Key"

• Some pathogens have a preferred portal of entry
• eg. Chlamydia trachomatis and mucous membranes
• Salmonella and the GI system

• Some pathogens have a preferred type of cell that they infect
• eg. Inflenza virus and respiratory epithelium with sialic acid residues
• Uropathogenic E. coli and urinary tract epitheium with D-mannose residues

• How the pathogen gains entry to the host
• (mucous membranes, skin, parenteral route)
• Some microorganisms have a "preferred" portal of entry (only capable of causing disease via a specific route

• One of the largest organs in body (surface area)
• Few organisms can breach the intact skin
• eg. hookworms
• Most organisms need a break in the skin to enter
• eg. S. pyogenes
• Some bacteria can enter through the sweat glands and hair follicles in the skin
• eg. S. aureus, P. acnes
• Some fungi eg. dermatophytes like Microsporum canis can grow on the skin

• "body as a tube"
• Respiratory tract (easiest and most common, inhalation)
• GI tract (food, water, hands; most organisms destroyed by acid or bile)
• Genitourinary tract (STDs)
• Conjunctiva

• Organisms gain access via broken skin
• Injections, punctures, bites, cuts, wounds, surgery, cracking/splitting of skin

• ie. Microbes that produce toxins that get into cells and cause the disease process-
• Corynebacterium diptheriae, Vibrio cholera, Bordetella pertussis

• A measure of pathogenicity
• Lethal dose for toxin: level where 50% of the hosts will die

Number of organisms required to cause disease in 50% of inoculated animals or hosts under defined conditions

• 1. Capsules
• 2. Cell Wall Components
• 3. Enzymes
• 4. Superantigens
• 5. Toxins
• 6. Invasins
• 7. Pathogenicity Islands, Type III secretion
• 8. Antigenic variation
• 9. Intra/extracellular growth
• 10. Transfer of Genetic Material (eg. Antibiotic Resistance)

• Glycocalyx
• Initially prevents C3b from binding and the phagocyte from recognizing and ingesting the bacteria
• Also aids in adherence to host cells
• BUT, later; antibodies produced to the capsule enable phagocytes to ingest the organism
• Many bacteria and some fungi can produce capsules in the right environmental conditions
• eg. Streptococcus pneumonia, Streptococcuc pyogenes, Haemophilus influenza, Neisseria gonorrhoeae, Neisseria meningitides, E. coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Bacillus anthracis, Yersinia pestis, Crptococcus neoformans, etc

• eg. M protein
• Streptococcuc pyogenes: heat and acid-resistant protein in the cell wall that allows attachment of the bacteria to epithelial cells and inhibits phagocytosis
• eg. Mycolic acids
• Mycobacterium tuberculosis: waxy substances in cell walls make the bacterium resistant to digestion inside the phagocyte
• Fc receptors: some bacteria have Fc receptors in the cell walls so that Fc area of an antibody binds to that bacteria instead of the Fab section, which protects the bacterium from phagocytosis and the Fc portion of antibody is not available for binding to the phagocyte

• Leucocidin - destroys blood cells (eg. S. aureus)
• Kinase: (eg. Streptococcus Group A) - Break down fibrin and dissolve clots formed by the body to isolate the infection
• Hemolysin (Staph, Strep, Listeria, Clostridium) - Break down red blood cells (eg. Streptolysin S and O in Streptococcus group A)
• Coagulase: eg. Staphylococcus aureus (not epidermidis) - clots: converts fibrinogen (soluble) to fibrin (insoluble), clot can wall the bacteria off from the host defenses
• Collagenase: eg Clostridium - breaks down collagen (connective tissue)
• Lecithinase: destroy plasma membranes (eg. Clostridium perfringens)
• Proteases: inactivate antibodies and other body proteins (eg. Neisseria gonorrhoeae has IgA protease)

An exoenzyme that destroys blood cells (eg. S. aureus)

• An exoenzyme that breaks down fibirin and dissolves clots formed by the body to isolate the infection
• eg. Streptococcus Group A

• An exoenzyme that breaks down red blood cells
• eg. Streptolysin  S and O in Streptococcus group A

An exoenzyme that clots: converts fibrinogen (soluble) to fibrin (insoluble), clot can wall the bacteria off from the host defenses

• An exoenzyme that breaks down collagen (connective tissue)
• eg. Clostridium

• An exoenzyme that destroys plasma membranes
• eg. Clostridium perfringens

• An exoenzyme that inactivate antibodies and other body proteins
• eg. Neisseria gonorrhoeae has IgA protease

• Test to see if Collagenase is present.
• Rabbit plasma and bacteria are put in a test tube. Fibrinogen (soluble) is present
• Then incubated.
• If there is a cot of the bottom the test is positive; Fibrin has been formed (insoluble)
• If no clot, it is negative; No fibrin

• Staphylococcus aureus = coagulase producer
• Staphylococcus epidermidis and other staphylococci are negaitve

• Necrotizing factors: kills body cells
• Hypothermic factors: decrease temperature
• Siderophores: scavenge and bind iron: most bacteria need iron to grow and exhibit virulence. (eg. lactroferrin sequesters iron which are needed for the bacteria in dental plaque, so increases levels of lactoferrin inhibits development of biofilm

• Also called Type 1 toxins (exotoxins)
• Protein antigens that stimulate a very large immune response: normally <1% of immune cells are activated by an infection, but if there is a superantigen as an activator, then the response can be measured in up to 20% of all lymphocytes
• Results in excessive release of cytokines: this will result in nausea, fever, diarrhea, shock, death
• eg. Staphylococcus aureus TSST-1 toxin which causes toxic shock syndrome is superantigen

• Often a primary virulence factor
• Usually proteins that can produce fever, cause heart failure, diarrhea, edema or shock
• Can destroy cells as well as inhibit protein synthesis, leading to cell death
• Two major types:
• Exotoxins including superantigens: exotoxins can be produced by some Gram (-) and some Gram (+)
• Endotoxin = LPS, Lipid A moiety: ***Endotoxin in found in Gram-Negative cell walls ONLY

• Part of the outer cell wall of Gram-negative bacteria-lipopolysaccharide (LPS)
• LPS = polysaccharide and lipid A (endotoxin)- this is heat stable
• Chills, fever, weakness, aches, shock and death
• Activates blood clotting system (DIC) (disseminated intravascular coagulation)
• Shock: life-threatening loss of blood pressure (if caused by bacteria called septic shock and if caused by Gram negatives called endotoxic shock)

• Produced by certain types of bacteria and released into the tissues (can be G+ of G- bacteria)
• Genes for exotoxins are carried on bacteriophages or plasmids (eg. diphtheria toxin, tetanus toxin)
• Proteins: 3 types based on function: cytotoxins neurotoxins, enterotoxins
• Very potent, but most are heat labile (5 min boil)
• Body produces antibodies called antitoxins to neutralize exotoxins
• Common with A-B toxins where A is toxic nd B binds to cells: 2 mechanisms, either diretly transferred into cytoplasm, or bound toxin is endocytosed and then transferred brom the endosome to the cytoplasm

• Botulism
• Tetanus
• Gas gangrene
• Diphtheria
• Whooping cough
• Listeriosis
• Necrotizing fasciitis
• Cholera
• Hamburger Disease, etc

• Surface proteins on some bacteria which activate actin (cytoskeleton of cell)
• Rearranges and allows bacterial penetration of the cell: eg. pedestal formation with Salmonella and pathogenic E. coli
• Some bacteria use their invasins to move from one host cell to another (eg. Shigella and Listeria)
• These bacteria infect intestinal epithelial cells laterally and evade the immune cells and host antibody

• Some bacteria, especially the G- have genes encoded on their chromosome that code for pathogenic attributes, eg. coding for a Type III secretion apparatus
• Type III secretion apparatus enables a bacterial cell to inject proteins into a host cell, killing or altering it.

• "Fooling the immune system": pathogens have antigens on their surfaces to which B cells produce antibodies
• Some pathogens change the makeup of their antigens = new pathogen (old antibodies not effective): eg. Neisseria gonorrhoeae has on Opa gene in several copies, which can emerge (be expressed) as needed. The Opa gene codes for surface antigens
• Some organisms can use host cell antigen to cover themselves and hide from host immune defenses

• Obligate Intracellular Bacteria: can only grow inside of host cells, often in a protected vacuole: eg. Chlamydia, Rickettsia
• Facultative Intracellular Bacteria: bacteria that can multiply outside of host cells, but often use intracellular growth as a means of evading the host defenses: eg. Bordetella, Mycobacerium, Salmonella

• Bacteria can mutate or take up small pieces of DNA that can change their virulence
• These pieces of DNA can either be integrated into the bacterial chromosome or exist as free floating genes in the bacterial cell
• These pieces of DNA can also be transferred between individuals; do not have to be of the same species
• This is an evolutionary advantage for pathogens
• Genes are often transferred on "Plasmids"
• Plasmid: small circular DNA molecules separated from the main bacterial chromosome
• One group, called the R factors, are responsible for transferring the genes for antibiotic resistance
• Plasmids may also encode for other virulence factors, for example toxin, Staphylococcal enterotoxin, heat labile toxins of E. coli

• Conjugation: "mating" of two cells with transfer of plasmid or chromosomal DNA
• Transduction: transfer of DNA to a bacterial cell by a virus (bacteriophage)
• Transformation: purified DNA taken up by cell

Small circular DNA molecules separated from the main bacterial chromosome

a group of plasmids that are responsible for transferring the genes for antibiotic resistance

• 1. Can inhibit macromolecular synthesis eg. stop mitosis
• 2. Can down regulate MHC I
• 3. Syncytium formation: some viruses, eg. RSV: host cells fuse together making a large multinucleate cell
• 4. Can deregulate cell function, eg. affect hormone production
• 5. Induce chromosomal changes in cells, eg. oncoviruses

• Infected cells fuse to form a giant cell with many nuclei
• Permits viral multiplication without exposing virus to antibodies eg. RSV, measles
• Leads to dead tissue

• Animals and humans are free of microbes in utero, acquire bacterial populations at and after birth
• Newborns first contact with bacteria is usually lactobacilli from mothers vagina
• With breastfeeding and exposure to the environment, foods and people other types of organisms are able to colonize their skin and intestinal tracts

• Respiratory: Streptococcus species (mostly alpha hemolytic)
• GI: Bacteroides fragilis
• Skin: S. epidermidis
• Vagina: Lactobacilli

• Microorganisms that may be present on body surfaces temporarily (days, weeks, months), then disappear
• Removed by handwashing (soap and mechanical scrubbing)
• Can be either pathogenic (disease causing) or nonpathogenic
• Do not necessarily cause disease unless special conditions prevail

• Relationship between normal flora and the host
• Commensalism: one of the organisms is benefited and the other not affected
• Mutualism: benefits both organisms
• Parasitism: one organism is benefited, the other is not and (can call this a pathogen)

• Microbial antagonism
• Normal flora prevent the overgrowth of harmful microorganisms
• Involves competition for nutrient, cellular receptors, production of substances that affect pH and available oxygen
• If the balance is upset, disease can result

A microorganism that can cause a disease process

• Always cause disease even in healthy immunocompetent individuals
• Never normal flora

• May cause disease only if given the right circumstances
• Can be normal flora

• Reservoir of infection
• Mode of transmission
• Susceptible host

• Continual source of disease organism
• Reservoir can be anything that can support growth of the organism (human, animal, non-living (soil, water, food))

• Disease transmitted to humans from an animal: animal may be healthy carrier or may be diseased, human is an "accidental host"
• eg. Rabies, Tularemia, Chlamydia psittaci, West Nile Virus and other arboviruses

• Horizontal transmission: transmission from one person to another through contact, ingestion, vectors, etc (eg. chicken pox, strep throat)
• Vertical transmission: transfer of a pathogen from a pregnant woman to her fetus, eg. Streptococcus group B from the vaginal canal, HIV from breast milk

• 1. Contact transmission:
• a. Direct contact: person-to-person eg. kissing touching, sexual intercourse
• b. Indirect contact: agent transferred from reservoir to the susceptible host by a non-living object eg. fomites like towels, drinking cups etc
• c. Droplet transmission: microbes are spread in droplets (mucus droplets) that travel up to 1m in air eg. sneezing produces ~20,000 droplet nuclei
• 2. Vehicle transmission: transmission of infection by a medium= food, water, air, blood, IV fluids: eg. Hepatitis B by blood transfusion, M. tuberculosis - airborne
• 3. Vectors: arthropods
• a. Mechanical transmission: passive transport on the vector's body eg. spread of Shigella infection on house-fly feet
• b. Biological transmission:  part of the life cycle of the microorganism is in the arthropods body, eg. Malaria and Anopheles mosquitoes: arthropod ingests agent -> agent multiplies in arthropod -> arthropod bites animal or human -> TRANSMISSION

Study of when and where disease occur. Purpose is to control disease transmission

Diseases which physicians and laboratoris are required to report to Public Health

Number of diseases occurring within a specified time period

Number of diseases in the population at a particular time period

Incidence of specific diseases

Number of deaths from diseases

Gonorrhea, Syphilis, Chlamydia trachomatis, Tuberculosis, Pertussis, Meningococcal meningitis, Malaria, Hepatitis A, Hepatitis B, Hepatitis C, HIV, Legionellosis, Leprosy, Hantavirus, Tetanus, Tuberculosis, Typhoid fever, Tularemia, Trichinosis, Yellow fever, Invasive Streptococcus group A disease, Etc

• Hospital acquired infections
• Type of infection
• Urinary tract (54%)
• Skin infections (22%)
• IV caused bacteremia (14%)
• Lower Respiratory (13%)
• Surgical Site (17%)

• Other patients
• Hospital Environment
• Health Care Professionals
• Patient's Own Normal Flora
• Visitors

• Serious illness or death
• Prolonged hospital stay
• Expensive antimicrobials may be needed
• Patient may become a carrier or source and spread the infection in the community

• Growing problem in health care institutions
• MRSA (methicillin resistant Staphylococcus aureus), VRE (vancomycin resistant enterococci), XDR-TB (multi-resistant M. tuberculosis), etc.
• Hand washing and adherence to hygienic routines is the only way to curb the epidemic

• A number of diseases are particularly and pose a risk for healthcare workers involved in the primary care of these patients
• Some of the more serious of these disease are:
• HIV, Hepatitis A,B,C, Norovirus, TB and other respiratory pathogens, Hemorrhagic fever viruses (eg. Lassa fever, Ebola), Tularemia, Plague, SARS

• Infected patients
• Soiled bedding, towels, dressings, other fomites
• Contaminated needles
• Surgical equipment

• Hand washing: the number one preventative measure
• Gloves, gowns, masks, goggles
• Proper handling of used needles
• Disinfection of the environment

• Immediately:
• 1. Wash needlesticks and cuts with soap and water
• 2. Flush splashes to the nose, mouth or skin with water
• 3. Irrigate eyes with clean water, saline or sterile irrigants
• 4. Report the incident to your supervisor
• 5. Immediately seek medical attention: in the case of HIV, anti-retrovira therapy may be indicated and this must occur within a short period of time; in the case of Hepatitis A or B, this may necessitate immediate vaccination or immunoglobulin therapy