Host Microbe Interactions

Question 1

Normal (Commensal) Microbiota in Humans

Answer 1

• normal microbiota have specific niches (anatomic sites of the host)
• normal microbiota synthesize and excrete vitamins that be absorbed as nutrients by the host
• contributes to the first line of defence against incursion by foreign microorganisms
• occupying surfaces/receptors
• producing inhibitors
• competing for nutrients

Question 2

Under what conditions can a commensal microbe be an opportunistic pathogen (4)

Answer 2

• immune competency compromised or deficient
• presence in unaccustomed sites, not the normal niches
• broad spectrum antibiotic therapy
• medical/dental device or implants

Question 3

Strategies employed by pathogens in avoiding host immune system (6)

Answer 3

1. Protective structural components and products
2. mimicry of host antigens
3. antigenic variation-changes in antigenic determinants
4. suppression of host responses
5. survival in macrophages
6. Grow in areas isolated from immune responses (surface of ducts, tubules, gallbladder)

Question 4

Diseases caused by S.pyogenes

Answer 4

• pharyngitis (strep throat), scarlet fever, impetigo
• sepsis, toxic shock syndrome (strepTSS)
• necrotizing fasciitis
• post streptococcal disease (rheumatic fever, glomerulonephritis)

Question 5

Regulation of virulence factor expression in S. pyogenes (3)

Answer 5

1. Stand alone response regulator MgA (multiple gene activator)
   - required for virulence gene expression (M protein, C5a peptidase, Ig binding proteins)
2. CovRS 2 component reg system
   - negatively regulates capsule synthesis, cys protease, streptokinase, streptolysin, DNase production
3. CcpA- genes normally repressed by HPr-P/ccpa complex can now be transcribed-altered virulence factor production

Question 6

Salmonella Enterica

Answer 6

• gram neg motile rods
• poultry products are main reservoir
• causes typhoid fever and salmonellosis
• enters body via GI tract, binds and invades intestinal epithelial cells, spreads to underlying tissues
• membrane ruffling as a result of actin reorganization by the spoE protein

Question 7

Salmonella-passage through the stomach and intestine

Answer 7

• during passage through the stomach, the bacterium survives acidic pH by eliciting acid tolerance response
• once in intestine, colonizes the distal ileum, enters underlying mucosa or lymphoid tissue either via invasion of epithelial cells or uptake by M cells
• once penetrated the epithelium, it is readily engulfed my macs but survives within the macrophages

Question 8

Salmonella Invasion

Answer 8

• cell invasion requires the production and transport of secreted effector proteins by a type III secretion system
• encoded in a salmonella pathogenicity island
• effector proteins are injected into host cells via the needle complex
• effectors (spoe) alter host cell cytoskeletal structure (actin rearrangement) resulting in engulfment of the bacteria

Question 9

Survival within macs

Answer 9

• two 2 component reg systems (PhoPQ and PmrAB)
• PhoQ activated by acidic pH and cationic antimicrobial peptides
• phosphorylated PhoP binds to DNA to control expression of phoP activated and phoP repressed genes
• leads to resistance to cationic antimicrobial peptides, phagosome alteration and intracellular survival
• PhoPQ regulates other virulence traits (cell invasion, acid tolerance, bacterial surface remodelling-LPS modification)

Question 10

Bacterial Surface Remodelling

Answer 10

-mask phosphate groups with positive charged moieties to avoid killing by CAMPs