Salmonella enterica Flashcards
Range of salmonella?
Broad
What dos it cause
Foodborne gastroenteretis, typhoid fever
What is a serotype
Variation between species of vacteria for causing disease
Typhoid serovars are
S. enterica, sub.enterica, typhi OR paratyphi
They are human-restricted
Non-typhoid serovars are
S. enterica, sub. enterica, tiphimurium
Broad range
This is model to study in labs
What are the problems of chronic carriage of salmonella (3)
1) bacteria shed toothers
2) antibiotics cannot clear everything
3) You can have salmonella ithout even knowing it
Antibiotics towards S. enterica
Are mq (transcription)
macrolides
quinolones
Resistance is a problem
Does drug resistance only occur in humans?
No, in envrionment as well
What’s different between S. enteria, subs enterica, TYPHI and THYIMURIUM
Typhi (human restricted) has WAYYY more pseudogenes (non-functional proteins)
What are the two pathogenicity islands that code for secretion systems
SPI1 and SPI2 code for T3SS, for early and late infection
Effector proteins are released through the T3SS
What are the names of the vacuoles where Salmonella stays?
SCV
Where does salmonella enter the body?
in the instestinal eptithilium.
Depending on the serotpye, it will enter different cells (usually non-phagocytic)
What does SPI1 do?
promote entry into non-phagocytic cells
What does SPI 2 do?
Promote surivival, replication and cell-cell spread
Give the 5 steps of salmonella infection?
- Before infection, it will trigger its early SPI-1 (T3SS) to deliver effector proteins to the host
Allows the ruffle of the host membrane – allows bacteria to enter host, Vacuole is made - It will interact with the endocytic pathways
- It will turn off SPI-1 and turn on SPI2.
- It will then target the lysosomal pathway through its SPI2 effectors
- There is also formation of tubules SITS. SITS are used to allow the bacteria to go back to the cell periphery
How does salmonella enter non-phagocytic cells?
SPI1 T3SS will deliver effectors similar to host proteins
They will activate Rho GTPases. These will allow for cytoskeleton rearrangement
This will afterwards need to be turned off to complete uptake
Which small GTPase allows for uptake to happen?
Rho (of Ras superfamily)
4 effectors control uptake? What do they do?
3 of them activate GEF or they mimic GEF
One is a GAP mimic to turn off uptake
How do SPI1 effectors suppress autophagy (sopF)
SopF of SPI1 tagets initiation of xenophagy. Xenophagy was discovered this way
vacuole ATPase is deactivated, o it can’t bind to a complex to start autophagy
2 Reasons why SPI2 effectors control bacterial poisoning?
Intermediate infection: want to keep pathogen near Golgi for nutrient acquisition
Late infection: bring to cell periphery for cell-cell spread
Which SPI(s) affect autopahgy
Both SPI1 and SPI2
How do SseF and SseG contribute to intermediate infection?
They thetther the SCV to the Golgi membrane
Which motor protein helps with movement towards cell periphery
kinesin
What do GTPases on SCV do to help with movement
GTPases will bind to an adaptor protein to bind with either kinesin or dyenin
How does SifA make cell movement stay towards the golgi?
Connects with dyenin adaptor BLOC2
What is LAMP?
It’s a SCV marker
What does PipB2 do to make cell movement towards periphery? (2)
Interacts directly with kinesin adaptor SKIP
Interacts with light chain of kinesin itself
What is a SIT? What are their possible purposes?
salmonella induced microtubule
Cell spread, nutrient acquisition
Which effectors cause SIT (5)
SifA, PipB2, SOPD2 = manipulate host microtubules
SseF and SSeG = tethering to Golgi
How do SPI2 effectors SseF and SseG target autophagy?
They bind to Rab1 GTPase to inihibit an initiation complex
How does salmonella effectors target NFkB pathway? (2 proteins)
It inhibits gene expression by cleaving proteins of pathway p65 and RelB
How does SPI2 effectors suppress antigen presentation in DENDRITIC cells?
Affect microtubule formation - prevents loading from happening
Salmonella effectors affect MANY types of cells.
Evolution of SPI1 and SPI2 in enterica vs. bongori
SP1 is in both
SP2 is unique to enterica
What happened to effector proteins in typhi serotype?
Lost function of effectors - make it unique to human infections
Which GTPase is related to host broadness. What do the 2 effectors do to it?
Rab32
Effectors sopD2 and gtgE target Rab32 to stop it from working
What is special about typhi’s SopD2 and gtgE?
They are knocked OUT
So, for BROADNESS of hosts in typhiMURIUM, these two are requried
How does SopD2 of typhiMURIUM affect Rab32, to allow for host BROADNESS?
SopD2 acts as a GAP to inactivate Rab32 GTPase
How does s. TYPHI use virulence factors to target HUMANs only? (2 ways)
Has polysaccharide capsules (Vi antigen) on surface to evade immune detection
Secretes a Typhoid toxin (CdtB exotoxin) that causes DNA damage tp human cell targets specifially
