1.10. Bacterial Pathogenesis 1 Flashcards
pathogenicity
Capacity to cause disease
Organism needs to be able to:
- Transmit-(communicability) from one host/reservoir to another
- Survive-in the new host
- Infect-ability to breach the new host’s defences
- Be virulent-ability of a pathogen to harm a host
Opportunistic Pathogens
- Rarely cause disease in immune-competent individuals
- If immunological/ anatomic defences are compromised, these bacteria can cause disease
- Often normal flora
- Become pathogenic in the absence of normal defence mechanisms ±removal of competing bacteria (e.g. broad spectrum antibiotics)
- E.g. Coagulase Negative Staphylococci (CNS)
natural history of HIV-1 infection
- thrush
- oral hairy leukoplakia
- tuberculosis
- pneumcystis carnii pneumonia
- Histoplasmosis
- Coccidloidmycosis
- Cryptococcosis
- Toxoplasmosis
- Atypical herpes simplex virus disease
- crytosporidiosis
- Cytomagalovirus disease
- Mycobacterium avium complex disease
Primary Pathogens
- Able to cause disease in healthy immuno-competent individuals
- BUT may more readily cause disease in individuals with impaired defences
- E.g. Streptococcus pneumoniae
Virulence
- Usually a multitude of factors acting in a co-ordinated fashion to produce disease
- Genetically determined/ expressed
- Single virulence factor rarely sufficient to cause disease
- Not all strains of a particular bacterial species are equally pathogenic
Why does a bacterium need virulence factors:
- Colonisation: adhesion factors
- Invasion: allow uptake of bacteria into cells
- Survival and multiplication
- Avoidance of host defence mechanisms-capsules, M protein, resist phagocytosis
- Toxin production-endotoxins, exotoxins
Establishing infection
•Pathogen entry: skin, respiratory tract, gastro-intestinal tract, urinary/genital tract
•Some pathogens require specific contact
-e.g. Treponema pallidum (syphilis)
-Requires direct skin to skin contact
-Humans are the only host-they will die in the environment
•Source of infection: individuals with clinical diseaseor carriers
-Carrier: individuals in whom symptoms may be absent or relatively mild because the disease process is at an early stage or because of partial immunity to the pathogen (e.g. Typhoid Mary)
•Other pathogens may be able to infect humansand animals-e.g. Salmonella spp, Shigellaspp, Campylobacter spp
-Source of infection: contaminated food or water in the environment
•Animals:
-Reservoir of infection (animals are infected, but do not get sick)
-Source of environmental contaminatio
colonisation definition
the establishment of a stable population of bacteria in the host
what does colonisation require?
•Requires adhesion to a mucosal surface•This allows for a focus of infection to develop, which may lead to localised infection/systemic spread•Adhesion involves surface interaction between host cell receptors and adhesinson bacterial surface•Presence or absence of cell receptors contribute to tissue specificity of infection
what are the consequences of adhesion?
- Induces changes in bacterial expression
* Induces intracellular signalling pathways
what are the types of adhesins?
- fimbrial adhesins
2. non-fimbrial adhesins
fimbrial adhesins
- Thin, rigid, rod like structure
- Mediate attachment to cell
- Found in GP and GN bacteria
- E.g. E.coli colonization factor antigen I and II
non-fimbrial adhesins
•Protein or polysaccharide structures that are on the bacteria cell or excreted
•Found in GP and GN bacteria
•E.g. Teichoic acid-CNS
Flagella –Vibriocholerae
Binding to Fibronectin
- A complex human glycoprotein found in plasma, associated with mucosal surfaces and promotes adhesion functions
- Many bacteria use fibronectinfor adhesion purposes
Invasion
- Some bacteria are able to cause disease after colonisation
- Most bacteria need to invade cells/tissue
- Some bacteria which are able to survive within the host cell: Mycobacteria, Salmonella, Shigella, E.coli, Listeria, Neisseria species
Cell invasion
- Ability to avoid humoral defence mechanisms
- Provide a niche rich in nutrients
- Provide protection from other bacteria
Uptake into host cells
- Usually use phagocytic entry mechanisms
- Some organisms remain in the superficial cell layers e.g. Shigella spp.
- Others invade into deeper tissue e.g. Salmonella spp.
Role of cell receptors
- Availability of specific receptors defines the types of host cells involved
- Specific host receptors have been identified for some organisms
- E.g. M. tuberculosis –complement receptors on phagocytes
Avoid host defence
- Humoral immune responses
- Cell mediated immune response
- Complement
- Lysozyme
- Iron chelators-transferrin, lactoferrin
Capsule
Aids in avoiding phagocytosis examples: Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae
Streptococcal M Protein
Not a capsule but avoids phagocytosis in a similar manner
example:
Streptococcus pyogenes
Resistance to killing by phagocytic cells
- Prevention of phagosome-lysosome fusion (Mycobacterium tuberculosis)
- Able to prevent oxygen-dependent killing (Salmonella Typhi)
- Production of catalase to negate effect of toxin radicals (Staphylococcus aureus)
- Inhibits phagosome-lysosome fusion (Legionella pneumophila)
Antigenic Variation
Change of antigen or DNA sequence to avoid an immune response against that antigen (immune system unable to recognise) example: Neisseria meningitidis -PorA amino acid mutations -Switch off expression of capsule
