2. Mechanisms of Bacterial Pathogenesis Flashcards
What is the normal flora?
- A collection of species of microorganisms routinely found on/in a human or animal
- Mainly species of bacteria that are acquired at or shortly after birth
- Occupy particular niches
How do normal flora help with the health of humans?
Normal flora protect the host from disease by:
- Competing with invaders for space and nutrients
- Producing compounds that kill or inhibit other bacteria
- Controlling the growth of other commensal bacteria
- Aiding digestion
- Boosting immunity
- Regulating body weight
- Producing vitamins (B12 and K)
- Maintaining an acidic vagina
What is an opportunistic bacteria?
- A non-pathogenic bacteria that usually does not cause disease that can become an opportunistic pathogen in a specific environment e.g. different part of the body or in elderly and immuno-compromised people
What are pathogenic bacteria?
- Bacteria found exclusively in association with disease
Define:
- Pathogen
- Pathogenicity
- Virulence factor
- Pathogen: an organism able to cause disease
- Pathogenicity: a measure of the ability of an organism to cause disease
- Virulence factor: factor(s) required by the microorganism that allow it to cause disease
What are the 5 Koch’s postulates?
- Give a limitation for the first 4
- The microbe must be present in every case of the disease
- Limitation: some diseases may not require the organism to infect the host e.g. caused by ingested toxins - The microbe must be isolated from the diseased host and grown in pure culture
Limitation: Some microbes cannot be cultured in pure culture e.g. complex lifecycle with several vectors - The disease should be reproduced when a pure culture is introduced into a healthy (susceptible) host
Limitation: some organisms lose virulence when cultured on media - The microbe must be recoverable from an experimentally infected host
Limitation: requires a suitable model organism (some pathogens are human host specific) - Effective therapeutic and/or preventative measures should eliminate the disease
What are the 4 modern molecular Koch’s postulates?
Postulate 1: The virulence gene is always found in strains with the particular virulence phenotype
Postulate 2: The gene should be expressed when the pathogen is in the host
Postulate 3: Mutation (inactivation) of that particular gene abolishes (or reduces) the virulence phenotype
Postulate 4: Reintroduction of the gene reconstitutes the virulence phenotype
What are the 5 steps of pathogenesis (infection)?
- Enter the body
- Colonise the host (sometimes involves invasion)
- Evade host defences
- Multiply and disseminate
- Cause damage to host
What are the two main mechanisms of step 2. colonisation?
Adhesion: bacteria estabilishing themselves within the host usually involves adhesion and sometimes the formation of biofilms (complex associations of bacteria).
Is mediated by adhesins which can be: associated with pili/fimbrae, afimbrial adhesins or associated with bacterial capsules.
Invasion of host cells:
Some bacteria need to invade host cells (after adhesion) in order to survive. This process is mediated by bacterial invasins. Can be into cells (invasion) or through cells (transcytosis). Can be passive or active.
What is active bacterial invasion?
- Involves specific receptor/ligand interactions between bacteria and host
- It is a response mediated by the host in response to:
- Bacterial trigger (trigger mechanism): mediated from inside host cell in response to bacterial effector proteins being injected into the cell which causes membrane ruffling as the cell cytoskeleton changes arrangement. Mechanism used by E. Coli, Shigella and Salmonella.
- Cell surface/ligand interactions (zipper mechanism): activated cell surface receptors cause a reorganisation of host cell cytoskeleton. Mechanism used by Listeria
How to bacteria evade the complement system?
- Capsule (complement C3b cannot bind) e.g. steptococcus pneumoniae
- Degrading complement proteins such as C5a (e.g. Steptococcus pyogenes has C5a peptidase)
- Binding host antibodies by the Fc region (e.g. Staphylococcal protein A of S. aureus)
How do bacteria evade antibodies?
- Remain inside host cells e.g. Mycobacteria, Chlamydiae, to not elicit immune response
- Host Mimicry: Make capsules with sugars mimicking host surface glycoproteins, to not elicit immune response
- Coat surface with host proteins e.g. Protein A of S. aureus, to not elicit a host immune response
- Cleave antibodies e.g. N. gonorrhoeae cleaves IgA dimer
- Colonise a privileged site (with poor access to antibodies or not accessed by APCs) such as inside cells, skin, CNS, gall bladder
- Antigenic switching: Neisseria and Salmonella change capsular antigenicity
How do bacteria evade phagocytes?
- Avoid being recognised or inhibit internalisation: avoid opsonisation, form capsules or biofilms
- Kill phagocyte e.g. S. aureus leukocidin
- Inhibition of phagosome maturation (survive in the phagocome), can be achieved by: blocking fusion of lysosomes, blocking acidification, lysing phagosomal membrane etc.
How do bacteria overcome competition with commensals and the host for nutrients to multiply and disseminate?
- Secrete high affinity iron-chelators (siderophores) and have siderophore receptors to capture them once they have bound iron
- Express high-affinity iron-binding membrane proteins
- Express receptors for iron capture proteins used by host
- Express toxins (e.g. haemolysins) to release host iron
What is the difference between a direct and indirect effect of a toxin?
- Direct: secreted or cell-associated toxins with a direct cellular pathogenic consequence
- Indirect: damage to host is caused by an exaggerated immune response to the toxin- at site(s) remote from the toxin
