Lecture 10 - Bacterial Invasion Flashcards
Why might bacteria invade?
1)
2)
3)
1) Obligate intracellular parasite
2) Avoid immune system
3) Penetrate to deeper tissues
Two mechanisms of invasion
1) Zipper
2) Trigger (ruffling)
Host cell function exploited by zipper
Receptor-mediated endocytosis.
Host cell function exploited by trigger
Macropinocytosis
Which invasion mechanism does Listeria use?
Zipper
Basic principle of zipper
1)
2)
3)
1) High-affinity binding to host cell
2) Induces receptor immobilisation and crosslinking
3) Results in receptor-mediated endocytosis
Basic principle of trigger
1)
2)
3)
1) Resembles cell ruffling caused by hormones or hormones
2) Bacteria induces large-scale actin polymerisation, ruffles on host cell membrane
3) Macropinocytosis
Is Listeria monocytogenes Gram + or -?
Gram +
How does Listeria normally enter the body?
Food-borne
Soft cheeses
Why can Listeria be very dangerous?
Can cross maternoplacental barrier, blood-brain barrier
How does Listeria enter host cells? 1) 2) 3) 4) 5)
1) Zipper
2) Bacterial surface covered with internalin protein
3) Internalin binds to E-cadherin
4) E-cadherin binds to internalin all over bacterial surface, causing host-cell membrane to envelop bacterium (receptor clustering)
5) Bacterium is internalised
Proof of internalin effectiveness
Beads coated with internalin can invade cells
Another term for internalin
InIA
E-cadherin function
In tight junctions
Connects actin to structures external to cell
Is zipper or trigger more complex?
Trigger
Trigger uses far more proteins (~50) than zipper (as few as one)
Zipper is a passive process. Trigger is an active process
Bacterium that uses zipper
Listeria monocytogenes
Bacteria that use trigger
Shigella flexneri
Salmonella enterica
Is Shigella Gram + or-?
Gram -
Shigella spread
Person-person
Water-borne
Effects of Shigella infection
Bacillary dysentery
Bloody diarrhoea
How does Shigella differ from other E. coli?
1)
2)
1) Acquired virulence plasmid, pathogenicity islands
2) No flagella or fimbriae, to reduce inflammatory response from bacterial proliferation
Protein making up Shigella T3SS shaft
MxiH
What does MxiH do?
Makes up shaft of Shigella T3SS
Functions of ipaB, ipaC, ipaD
Inserted into host cell by Shigella, induce membrane ruffling (particularly ipaC)
Shigella proteins that induce membrane ruffling
ipaB, ipaC, ipaD
ipaC most important
Which cells does Shigella invade?
M cells
Host cell proteins activated by Shigella to polymerise actin
RhoGTPases
Does Salmonella use zipper or trigger?
Trigger
Host cell proteins targeted by Shigella
Actin, vinculin, tubulin (cytoskeletal proteins)
Proteins used by Salmonella to invade
Sip proteins, encoded on SPI-1
Proteins encoded by SPI-1
Sip proteins (for Salmonella) T3SS
Targets of Sip proteins
Host cell cytoskeleton, GTPases
Number of T3SS’s possessed by Salmonella
Two
What are the different Salmonella T3SS functions?
T3SS 1 - Induce host cell membrane ruffling
T3SS 2 - Escape from endosome, secrete Ssa
Ssa proteins
Effector proteins secreted by Salmonella T3SS number 2
SPI-1 effects 1) 2) 3) 4)
1) Invasion
2) Cytoskeletal rearrangements
3) Inflammation
4) Diarrhoea
SPI-2 effects
1)
2)
3)
1) Avoid intracellular antimicrobial defences
2) Modification of vacuole trafficking
3) Intracellular replication and survival
Broadly different roles of SPI-1 and SPI-2
SPI-1 - Invasion
SPI -2 - Intracellular survival
