Bacterial Virulence and Antibiotics Flashcards
What is the infectious process
- Bacteria adhere to host cells
- Establish primary site of infection (mircrocolonies)
- Spread through tissues or lymph to blood stream
- Reacg tissue suitable for multiplication and survival
BACTERIAL “NEEDS” FOR ESTABLISHING PATHOGENESIS
Factors that influence adherence
- Net surface charge (Bacteria and host cells generally have a negative net surface charge, so their interaction is somewhat repulsive…however, surface hydrophobicity helps to overcome repulsion)
- Surface hydrophobicity (The more hydrophobic the bacterial surface, the greater the adherence to the host cell)
- Presence of “appendages” which mediate receptor-ligand interactions (pili or fimbrae)
Obligate vs facultative intracellular
obligate intracellular (can only grow within host cell) or facultative intracellular (can grow within host cell and as free-living cells in the environment)
Ways bacteria escape the host phagocytic response
- Capsules (Usually polysaccharide polymers, some are protein)
- IgA1 protease (enzyme that cleaves IgA and inactivates its ability to provide mucosal immunity)
- Protein A (binds Fc region of IgG to prevent opsonization and phagocytosis)
- M Protein (expressed by group A streptococci)
- Intracellular growth - initiallyt invisible
Complement fixation
attachment of Ag/Ab complexes to “tag” the microbe for immune system recognition
Opsonization
“coating” of microbes by molecules to make it more “appealing” to phagocytes
Exotoxins and types
secreted proteins from G (+) and G (-) bacteria) that have direct toxic effects on cells); exception: exotoxin secreted from M. ulcerans is a lipid
Secretion systems def and types
Endotoxins
Lipid A portion of the lipopolysaccharide (LPS) in the Gram-negative outer membrane
Triggers inflammation by interacting with TLR4 on the host cell
Endotoxins vs exotoxins
Siderophores
iron-scavenging chemicals that tightly bind iron
Siderophores “trap” any available iron and may “strip” iron from transferrin and lactoferrin (if needed)
Tissue-degrading enzymes
not intrinsically toxic, but assist in different ways in the infectious process (e.g. collagenase: degrades collagen to assist in tissue spread; coagulase: contributes to fibrin formation which can help bacteria persist within the tissue and/or protect them from phagocytic destruction…)
Antigenic variation
Variation in surface antigens between bacterial species (can be markers for virulence, but may not be virulence factors)
Aspects of the drugs and drug classes that affect the antibiotic’s concentration in the infected tissue include:
- Half life
- Balancing concentration vs toxicity
- Oral absorption and bioavailability
- Tissue uptake, route of metabolism and elimination
- Metabolism or inactivation of the drug by resistant bacteria
