Bacterial Pathogenesis

Question 1

Define symbionts, commensals, and pathogens

Answer 1

Symbionts: beneficial bacteria (normal flora)
Commensals: Neither beneficial nor harmful (normal flora)
Pathogens: invade and multiply in normally sterile body compartments/assoc with tissue damage

Major distinguishing factor: pathogens have virulence factors, non-pathogens do not.

Question 2

What are the pathogenic mechanisms of tissue damage?

Answer 2

• Endotoxin-promoted inflammation (Endotoxins are found in gram-negative bacteria)
• Immune complexes
• Cell-mediated immunity eg activated macrophages in TB

Question 3

Ways that pathogens evade Toll-like receptors

Answer 3

Flagellin modification: Molecules not recognized by TLR5

Lipopolysaccharide modification: Yersinia pestis synthesizes LPS-lipid A with poor TLR4 stimulating activity at mammalian body temperature

Question 4

Bacterial evasion of complement system?

Answer 4

Bacterial expression of capsules allows them to resist complement-mediated lysis. Also express specific proteins on surface to recruit host complement regulatory proteins, to inactivate C3

Question 5

Ways in which pathogens evade phagocytosis?

Answer 5

1. Peptidoglycan deacetylation which confers lysozyme resistance
2. Presence of capsules, M protein and fibrin coats, which do not bind adhesion molecules used by macrophages and neutrophils
3. Fusion inhibition with lysosome or leaving the phagosome

Question 6

Ways in which pathogens evade antibodies?

Answer 6

1) Antigenic variation: organism alters its surface proteins to evade a host antibody response, antigenic diversity
2) Express proteases that specifically degrade antibodies: Neisseria menigitidis and Haemophilus influenzae produce extracellular IgA1 proteases that can cleave IgA1 to separate antigen-binding fragment (Fab) and Fc

Question 7

Parts of Type III Secretion System

Answer 7

An injectosome
Proteins needed to assemble the needle
Effector proteins that interfere with/subvert host response

Question 8

Describe the way in which effector protein in Yersinia works

Answer 8

Yersinia: YopJ deubiquitinates critical proteins in signal transduction, prevents TNF release from host cells, and blocks MAPKK with acetyl moieties which shuts down the immune response

Question 9

Describe the way in which effector protein use in Salmonella typhimurium works

Answer 9

SipA binds directly to actin and decreases actin concentration/inhibits depolymerization, facilitating bacterial uptake

Question 10

Describe the way effector proteins in EPEC/EHEC work

Answer 10

Form actin pedestals by injecting Tir molecules into plasma membranes of host cells, which when it interacts with intimin triggers said pedestal assembly.

Question 11

Why are Type III secretion systems genetically unique?

Answer 11

Many genes encoding TTSS are clustered (locus) and referred to as a -pathogenicity island- but absent in evolutionarily-related non-pathogenic bacteria

Indication of foreign origin due to G+C content differences