L22 signal transduction and virulence

Question 1

SALMONELLOSIS

Answer 1

gastroenteritis and enteric fever

caused by nontyphoid Salmonella

increased significantly in the last decade

Question 2

INFECTIOUS AGENT of salmonellosis

Answer 2

Salmonella enterica (serovar Typhimurium)
= S. typhimurium
intracellular pathogen

Question 3

Typhoid fever

Answer 3

a severe systemic disease of humans
caused by S. typhi

Research Model
- S. typhimurium
causes a similar disease in mice

Question 4

To survive and cause disease what must S. typhimurium (typhi) endure?

Answer 4

lysozyme in saliva
acid stomach 
alkaline bile salts
anaerobiosis
high osmolarity
low iron content

But also, acidic macrophage

Question 5

the type III secretory apparatus helps

Answer 5

Facilitate entry into M cells
Survival in phagosomes
Survival in macrophages

Question 6

SPI 1

Answer 6

large pathogenicity island includes inv & spa
virulence genes

encode a Type III secretory system
which exports Sip proteins through bacterial cell surface into the host M cell

Sip proteins facilitate invasion
e.g. ruffling

Question 7

Why dont lysosomes merge with the phagosomes and kill the bacteria

Answer 7

Type 3 secretory apparatus
Secretes proteins into the M cell cytosol
Inhibiting phagosome-lysosome fusion

Question 8

how does the pathogen enter the macrophage from the M cell

Answer 8

SPI 1 encodes a second secretory apparatus (prg gens) that exports proteins through bacterial cell surface into the macrophage. Facilitates phagocytosis by macrophage

Question 9

Two-component Signal Transduction

Answer 9

1. SENSOR (receptor)
   Histidine autokinase
   phosphodonor = ATP
   usually membrane bound

2. RESPONSE REGULATOR
(transcription factor)
Aspartate autokinase
phosphodonor = phosphorylated sensor
usually a DNA binding protein. can activate or repress

mammals do not have 2 component signal transduction
signal binds the receptor in the periplasm

Question 10

sip proteins

Answer 10

exported into M cells by the type III secretory apparatus to facilitate phagocytosis via ruffling and other changes to the eukaryotic cell.

Question 11

PhoQ

Answer 11

is a membrane bound histidine kinase sensor, that senses low Mg2+ concentrations

Question 12

PhoP

Answer 12

response regulator
DNA binding protein
phospho=PhoP represses genes required for invasion into M cells (prg) and macrophages and activates genes required for survival in the macrophage (pag)

Question 13

pag genes

Answer 13

PhoP activated genes
essential for: 
virulence in mice
survival in macrophages
resistance to antimicrobial peptides (defensins) produced by the macrophage
contain ASPs

Question 14

prg genes

Answer 14

PhoP repressed genes
essential for:
induction of endocytosis, including the type III secretory apparati used to invade both M cells (spa, inv) and macrophages (prgHIJK)

Question 15

PhoQP mutants

Answer 15

do not cause disease
do not survive in macrophages
are sensitive to low pHs
are sensitive to defensins

Question 16

the process of PhoQP signaling system

Answer 16

1. once engulfed by the macrophage the PhoQ senses low Mg2+ in the phagosome and autophosphorylates
2. PhoP uses phospho-PhoQ as a phospho donor and autophosphorylates
3. Phospho-PhoP activates pag genes and represses prg genes

Question 17

why is acid tolerance important virulence factor for salmonella

Answer 17

it must survive the acidity of the stomach and the phagosome

Question 18

Examples of VIRULENCE FACTORS CONTROLLED BY

2-COMPONENT SIGNALING

Answer 18

CHEMOTAXIS - Escherichia coli & others
PERTUSSIS TOXIN - Bordetella pertussis
CAPSULE - Pseudomonas aeruginosa

PhoPQ regulon - Salmonella typhimurium