L18: Signal Transduction and Virulence Flashcards

1
Q

What causes gastroenteritis and enteric fever?

A

Non-typhoid Salmonella

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2
Q

What causes typhoid fever?

A

S. typhi

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3
Q

What are the two acidic environments salmonella must survive?

A
  1. Stomach

2. Acidic phagocytic vesicle of the macrophage

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4
Q

After surviving the trip through the GI system, salmonella colonize the ___ and invade the ___. This occurs by bacterial-mediated endocytosis. What are the two steps of this process?

A

Small intestine; M cells; Attachment and entry

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5
Q

In contrast to V. cholerae, Salmonella is a ___ pathogen.

A

Intracellular

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6
Q

Describe the process of invasion by Salmonella.

A

Salmonella attaches to the vili of the M cell. The bacterium communicates to the M cell and causes growth of the vili; these engulf the bacteria (ruffling) into a phagosome in the M cell. It passes to the basal side and fuses with macrophages.

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7
Q

After macrophages engulf Salmonella, what happens?

A

Macrophages carry the bacteria to the reticuloendothelial system and from there into the bloodstream, causing a systemic infection.

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8
Q

What are Type III secretory apparati used for in infection by Salmonella?

A
  1. Facilitation of entry into M cells
  2. Survival in phagosomes
  3. Survival in macrophages
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9
Q

How does Salmonella facilitate entry into M cells using a Type III secretory apparatus?

A

SPI1 is a large pathogenicity island that includes inv, spa, and sip. inv and spa encode a Type III secretory system, which exports Sip proteins through the bacterial cell surface into the host M cell. Sip proteins facilitate phagocytosis via ruffling.

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10
Q

Why don’t lysosomes kill bacteria in phagosomes?

A

Type III secretory apparatus secretes proteins into the M cell cytosol and inhibits phagosome-lysosome fusion

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11
Q

How does the pathogen facilitate entry into macrophages?

A

Another Type III secretory apparatus (prgHIKL) exports proteins (EPs) through the bacterial cell surface into the macrophage. This facilitates phagocytosis by the macrophage.

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12
Q

Once inside the macrophage, how does S. typhimurium survive?

A

It represses genes necessary for entry and activates genes necessary to defeat macrophage defenses.

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13
Q

What are the two components of a 2CST (two-component signal transduction)?

A
  1. Sensor (histidine autokinase)

2. Response regulator (aspartate autokinase)

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14
Q

What happens when an environmental signal binds to a sensor kinase?

A

The sensor kinase is autophosphorylated (uses ATP). The response regulator is autophosphorylated (uses sensor kinase). The response regulator is typically a TF that either activates or represses transcription.

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15
Q

Each response regulator is attached to a ___.

A

Output domain (eg, DNA-binding domain)

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16
Q

What are some examples of virulence factors controlled by 2CST (and the relevant bacteria)?

A
  1. Chemotaxis (E. coli)
  2. Capsule (P. aeruginosa)
  3. Toxin (S. aureus, B. pertussis)
  4. Pili (E. coli)
17
Q

What is the relevant 2CST in salmonella? What is the sensor and response regulator?

A

PhoQP
Sensor: PhoQ
PhoP: response regulator

18
Q

What does PhoQ sense?

A

Low Mg2+ concentrations

19
Q

What does PhoP do when activated by PhoQ?

A

Represses genes required for invasion into M cells and macrophages (prg) and activates genes required for survival in the macrophage (pag)

20
Q

What does pag encode?

A

ASPs and anti-defensins

21
Q

How do we know that PhoPQ is required for virulence?

A

Mutants are avirulent, do not survive macrophages, and are sensitive to low pH and defensins