Salmonella III

Question 0

What are examples where salmonella outbreaks have occurred?

Answer 0

Salsa
Breakfast cereal
Cantaloupe
Frozen meals
Snack food
Peanut butter
Tomatoes
Foster farm chicken

Question 1

What happens in 10% of gastroenteritis cases from typhimurium?

Answer 1

Post-infectious arthritis (Reiter’s syndrome)

Question 2

Where does salmonella colonize?

Answer 2

Peyer’s patches–invade through M-cells

• gastroenteritis: induces neutrophil influx
• enteric fever: dissimination to lymph nodes, liver, spleen

Question 3

What is the role of PhoP/PhoQ in salmonella virulence?

Answer 3

PhoP activates SPI2 and inhibits SPI1 invasion

Question 4

What happens in a PhoP mutant?

Answer 4

Mutants

• 10,000x less virulent
• killed by anti microbial peptides
• failed to grow in macrophages

PhoP activated genes: Pags
PhoP repressed genes: prgs

Question 5

What’s an example of a prg?

Answer 5

PrgJ= inner rod in T3SS and activates inflammable through NLRC4…part of Spi1 T3SS

Question 6

What is the PhoPQ system?

Answer 6

It’s a two component system that regulates salmonella virulence through signals like ph=5.5, anti microbial peptides, Mg2+, or proteases

Question 7

What does PhoP do?

Answer 7

• lipid A remodeling
• anti microbial peptide resistance
• reduced innate immune recognition
• SPI2 activation
• SPi1 inactivation (no invasion)
• inhibits flagellar motility

Question 8

What are the characteristics of PhoP constituitive (PhoPc)?

Answer 8

Locked in active configuration and produce Pags but not prgs.

Virulence is the same as having no PhoP (less virulent with PhoP always on)

PhoP- didn’t immunize mice but PhoPc did.

Question 9

How does salmonella survive within a phagosome and replicate?

Answer 9

Typhimurium invades macrophage through SPI1, matures into a late SCV, PhoPQ is turned on since ph is low (5) and this turns on SPI2 and turns off SPi1, which then allows for intracellular growth.

Question 10

Why are mice without caspase-1 more susceptible to salmonella oral infection?

Answer 10

Salmonella activates NLRC4, which then activates cleavage of caspase-1 and inflammasome activation and therefore pyroptosis. No caspase-1, no pyroptosis.

Activation of NLRC4 is through secretion of flagellin through SPI1

To get pro-IL-1beta, LPS binds to TLR4, which allows caspase-1 to cleave it to get mature IL-1beta. Trigger of pyroptosis happens.

Question 11

What is capable of inducing inflammasome activation through salmonella invasion?

Answer 11

• Fla- minus salmonella still can induce reduced levels of pyroptosis.
• cuz prgJ also activates NLRC4 with or without flagellin.
• SsaI doesn’t activate (prgJ homology)

Question 12

What happens if you replace SsaI with PrgJ?

Answer 12

A virulent strain.

Control mouse to make conclusion: mouse lacking NLRC4

Question 13

What’s the consequence of caspase-11?

Answer 13

In cytosol, caspase-11 is activated by LPS….endotoxic shock

Question 14

Where do SopE/E2 come from and what do they do?

Answer 14

• Effector proteins from SPI1 T3SS.
• 70% identical with GEF activity
• SopE activates Rac and Cdc42
• SopE2 activates only Rac
• either is sufficient to mediate invasion.

Question 15

Where is SopE encoded?

Answer 15

On a lysogenic bacteriophage

Present in typhimurium strains associated with human disease

Question 16

How does SopE’s role in intestinal inflammation promote pathogenesis?

Answer 16

SopE activation of inflammation leads to production of nitric oxide➡️nitrate

This leads to nitrate being a terminal e- acceptor and leading to anaerobic respiration, which promotes growth of salmonella selectively compared to other intestinal microbes.

So, SopE➡️nitrate➡️anaerobic respiration ➡️selective growth advantage in intestines