Module 24 - Bacterial Pathogenesis Flashcards
Mention the Koch’s Postulates.
- The organism must be associated with the disease and its characteristic lesions
- The organism must be isolated from the diseased host and grown in culture
- The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.
- The same organism must be reisolated from the experimentally infected host.
What are Obligate pathogens?
Bacteria’s that can only reproduce in the host’s cell
Mention Molecular Koch’s Postulates.
- The phenotype or property under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species
- Specific inactivation of the gene(s) associated with the suspected virulence train should lead to a measurable loss in pathogenicity or virulence
- Reversion or allelic replacement of the mutated gene should lead to the restoration of pathogenicity
Mention the attributes of a pathogen.
- Colonisation (via adhesion)
- Penetration
- Multiplication
- Tissue damage
- Disease
Differentiate between association and adhesion
How is colonisation (via adhesion) occur between bacteria and the target cell,
Adhesion is mediated by surface proteins: Fimbrae/pili or Adhesins (outer membrane proteins).
Fimbrae/pili may bind with oligosaccharides located in the host cell glycoprotein. Other than that, the host cell may also have receptors that bind with adhesin from the bacterial cell. Both assist in cell-specific adhesion.
Entry of pathogenic pathogen involves penetrating through __________. This may happen either ________ or _________ the cells.
epithelium, through and between
Mention an example of how a bacteria may invade the human cell.
Yersinia may invade the M cell in the intestinal tract through the use of invasin protein. The invasins interact with the integrins of the M-cell, forming a vacuole that endocytoses the bacteria inside the cell.
Outcomes of bacterial invasion.
Explain bacterial strategies in overcoming phagocytosis.
Strategies include:
- Direct evasion of phagocytosis
- Or interfering with opsonins (a substance that binds to a micro-organism for phagocytosis), such as antibodies, complement, lectin, etc
Explain the pathways of complement activation.
First innate immune signalling in response to infection
- Classical pathway: Antigen-Antibody Complex interaction
- MBL (Mannose-binding ligand) pathway: recognizing mannose in the surface
- Alternative pathway: recognizing pathogen surface - PAMP such as LPS
Cascade of proteins that are activated. One of those proteins is C3b which allows opsonisation (promote phagocytosis)
Explain how bacteria achieve complement evasion.
Bacteria have surface proteins that bind C4BP or FH protein that are responsible for the degradation of the complement proteins. It can also sequester/inactivate C3 complement.
Bacteria may also secrete proteases that specifically degrade complement protein.
Explain the mechanism of direct evasion of phagocytosis.
- Bacteria (S. aureus) may produce leukocidin molecules which bind to the receptor and interact with each other to form pores in the phagocyte - inducing cell death.
- Capsule (sugar) is a specialised structure that prevents phagocytosis. Hyaluronic acid component resembles host structures.
Explain the mechanism of phagocytosis.
How do capsule enhance virulence?
Capsule enhance virulence by:
- Resemble host components (Hyaluronic acid)
- Mask underlying structures
These characteristics prevent the opsonisation of the bacteria. However, antibodies can be used to provide a binding site for complements (bypassing bacterial capsule capabilities)
Mention the three mechanisms of which intracellular bacterial pathogens can resist killing by phagocytes.
- Inhibit the respiratory burst
- Prevent phagolysosome formation
- Escape from the phagocytic vacuole
- Resist bactericidal system
Compare between exotoxins and endotoxins.
Toxoids: an inactive form of toxin that still possesses their antigenicity
Ab: antibodies
Antigenicity: the
capacity of a chemical structure (either an antigen or hapten) to bind specifically with a group of certain products that have adaptive immunity:
Describe the biochemical structure of an intracellularly-acting exotoxins.
Many have a bifunctional structure (A-B), where the A subunit is the active part with enzymatic activity, while the B subunit is responsible for the binding to the target cell.
Explain how an A-B toxin (such as Diphtheria toxin) can cause tissue damage.
The toxin’s binding domain (B) binds to host membrane (through toxin receptor), allowing to enter through endocytosis. The subunits are then cleaved, but still, hold on to each other by disulphide bonds.
When the vesicle acidifies, the disulphide bonds are reduced, allowing the catalytic A peptide subunit to pass through to the cytosol.
The domain then ADP-ribosylates EF2 (addition of ADP-ribose), which halt protein synthesis and kills the cell.
