invasion Flashcards
mechanisms of invasion
zipper: receptor mediated endocytosis, triggers actin rearrangement
trigger: contact triggers
large scale actin polymerization and formation of ruffles on cell surface, ruffles fold over and engulf bacteria- macropinocytosis
What uses zipper mechanism + steps
listeria monocytogenes
1. InlA interacts with E-cadherin
E-cadherin + InlA interactions causes receptor clustering
- Clustering causes actin cytoskeleton changes
- Leads to membrane curvature
Engulfment of organism
How many invasins does listeria have
InIA and InlB
Differences in human/animal receptors leads to differential infectivity/ability of Listeria to bind and invade
Reason why we don’t have a good animal model
E-cadherin
- numerous on epithelial cells
involved in tight junction formation
What uses trigger mechanism
shigella flexneri
salmonella
Shigella flexneri
- Passes through M-cells (resident cells that line the lumen that sample the environment inside the gut)
- Ends up inside macrophages associated with M cells
- Induces cell death in macrophages
- From basal membrane, can then invade epithelial cells from the sub-mucosal side and undergo intracellular life cycle
BUT, this is also an alarm to the host!!
- Recruitment of immune cells causes the tissue damage that is associated with infection
shigella T3SS
effector protein
IpaC and D form channel that allow entry of effector proteins
IcaC triggers actin regulation machinery that alters host cytoskeleton
Trigger mechanism - Salmonella
- SPI-1 invasion - encoded on Salmonella pathogenicity island 1
T3SS whose effectors induce membrane ruffling
coxiella burnetti
intralysosomal
cause Q fever
associated with animal products
coxiella burnetti life stages
taken up by phagocytosis
in a vacuole (CCV), is a small cell variant (heat stable and metabolically inactive)
fuses with lysosomes
grows optimally at pH<5
SCV become large cell variant (LCV)
Metabolically active form
T4SS starts secreting effectors: regulate vesicular trafficking, apoptosis, inflammasome activation, etc
cytosolic pathogens steps
- Invade cells
- Escape vacuole and proliferate
- Recruit host cell cytoskeletal proteins, induce actin polymerisation
“hitch a ride on host cytoskeleton” - formation of actin tail
- propel bacteria into adjacent cell
cytosolic pathogens
Listeria
Listeria escapes vacuole with listeriolysin O (LLO) – pore-forming toxin
ActA mimics host protein WASP
Shigella
- Shigella uses IcsA
- IcsA recruits N-WASP
WASP
WASP regulates cytoskeleton dynamics
Recruits Arp2/3, makes branched actin filaments drives actin polymerisation
Intravacuolar pathogens
Legionella pneumophila - life cycle
- g-, aerobic rod
lives inside vacuole, secretes effectors with a type IV secretion system
effectors prevent lysosome fusion with their own vacuole
recruits vesicles from ER and mitochondria
