Invasion Flashcards
pathogen invasion (3)
- pathogens can enter and survive in host cells
- allows them to breach host epithelial barrier
- provides them with protected niche for replication and persistence
pathogen mechanism of invasion (2)
- can actively direct their entry into host cells
- usually done by a protein called “invasin”
invasins (2)
- activate a receptor
- leads to a signaling event that enables uptake through cytoskeletal rearrangements
mechanisms of particle update into cells (2)
- zippers
- triggers
mechanisms of particle update into cells: zippers (3)
- sequential engagement of phagocytic membrane with particle surface
- pseudopod advances no further than receptor-ligand interaction permits
- partial engulfment where receptor-ligand interactions are
mechanisms of particle update into cells: triggers (2)
- all-or-nothing effect
- complete phagocytosis
zipper uptake steps (4)
- initial contact (adherence)
- receptor clustering
- phagocytic cup formation involving actin polymerization and membrane extension
- closure of phagocytic cup and retraction involving actin depolymerization
Yersinia (2)
- enteric pathogens that infect Peyers Patches in the intestine
- pathogenesis involves translocation across intestinal barrier via M cells, an easy cells for bacteria to breach
M cells (2)
- epithelial cells that lack mucus on their surface and lack microvilli
- sample their environment and take up particle nutrients and microbes
Yersinia and Invasion: what mechanism does Yersinia use for invasion
- zipper-mediated invasion
Yersinia and Invasion: how does Yersinia access enterocyte cells
- Yersinia translocated through M cells and enters neighbouring enterocytes via the basolateral membrane
Yersinia and Invasion: what proteins are involved in Yersinia invading enterocyte cells (2)
- invasin protein involved in entering enterocytes
- binds integrin receptor only expressed on basolateral side of enterocytes
Yersinia and Invasion: when is invasion acheived
- when there are sufficient numbers of receptors bound to the invasin through zipper-medicated uptake
How is Yersinia competing with ECM proteins
- integrin receptors bind ECM proteins and use actin to remain in proper formation
Yersinia and Invasion: invasin and ECM affinity to integrin (2)
- affinity of integrin for invasin is very high
- affinity for invasin is 100x higher than affinity for ECM proteins
Yersinia and Invasion: what occurs as a result of the sufficient amounts of integrin bound to invasin (3)
- tyrosine phosphorylation
- involves FAK (kinase), PI3 kinases, GTPases Src and Rac
- cytoskeletal rearrangements and pseudopod engulfment result
Listeria monocytogenes and Invasion: what mechanism of invasion
- zipper-mediated invasion
Listeria monocytogenes and Invasion: invasin ligand and receptor in enterocytes (2)
- the invasin is Internalin A (InlA)
- the receptor is E-cadherin
Listeria monocytogenes and Invasion: invasin ligand and receptor in hepatocytes (2)
- the invasin is Internalin B (InlB)
- the receptor is a protein called “Met”
Listeria monocytogenes and Invasion: what does uptake involve
- involves clathrin-mediated endocytosis and cytoskeletal rearrangements
trigger uptake mechanisms (3)
- mechanism similar to micropinocytosis
- macropinosomes
- surface ruffling
trigger uptake: mechanism similar to micropinocytosis
- a form of endocytosis that is accompanies by cell surface ruffling
trigger uptake: macropinosomes
- large vesicles that serve as a route for cells to take up macromolecules non-selectively
trigger uptake: membrane ruffling (2)
- unguided pseudopodia
- ruffles fall back onto bacteria and this leads to formation of large endosomes, which eventually become smaller
trigger: distinct steps (3)
- filopode formation: membrane ruffles
- lamellipode formation: membrane ruffles filled with actin support through polymerization
- formation of phagocytic cup made of actin or through adherence
Shigella flexneri (3)
- originates from the colon and is extremely infectious
- initially invades M cells
- causes “bloody” diarrhea and inflammation, which is crucial for its pathogenesis
Shigella and Invasion (2)
- involves over 30 bacterial proteins that mostly encode T3SS apparatus, while the rest are effectors
- hijacks normal cell signaling pathways to cause massive cytoskeletal rearrangements
Shigella Invasion: trigger step 1 (3)
- bacterial proteins IpaB and IpaC form pore in host cell membrane (T3SS) and serve as ligands for host cell receptors
- this becomes a portal for effectors to enter the host cell
- triggering results in local destabilization of microtubules by Shigella protein VirA
Shigella invasion: trigger step 2 (3)
- activation of cell signaling occurs via many GTP-binding proteins such as CDC42/Rac
- leads to lamellipode formation
- several host proteins are involved in mediating actin polymerization and cytoskeletal rearrangements
Shigella invasion: trigger step 3 (2)
- final step is actin depolymerization mediated by Shigella protein IpaA
- IpaA binds host protein vinculin to induce actin depolymerization, resulting in Shigella uptake
zipper vs trigger (2)
- zipper results in localized contact-dependent receptor-medicated particle engulfment
- trigger results in generalized engulfment event that could include neighbouring particles
anti-phagocytosis (2)
- some bacteria actively inhibit their uptake
- secrete protein YopH through T3SS
YopH
- phosphatase that overrides kinase that is activated by invasin
can one pathogen exhibit both zipper and trigger mediated invasion
- yes, for instance, salmonella can invade host cell using different routes and mechanisms
