11. Bacterial exploitation of host cytoskeleton and intracellular trafficking Flashcards
(48 cards)
What has allowed pathogens to be able to manipulate host cells?
Intimate involvement between pathogens and host
What cellular processes can bacteria exploit?
- Cytoskeleton dynamics
- Membrane trafficking
- Phosphoinisitol lipid metabolism
- Post-translational modification
- Apoptosis
- Intercellular adhesion
- Proteolysis
- Inflammatory responses
- Cell division
- Autophagy.
- cell motility
What makes up the cytoskeleton?
- Microtubules
- Intermediate filaments
- Microfilaments - actin
What are microtubules?
- Made of tubulin
- 25nm diameter
- Important in moving things around cells.
- Can be disrupted by Shigella, salmonella, and campylobacter
What are intermediate filaments?
- Made of cytokeratin and vimentin
- 10 nm diameter
- Less bacteria interact with these but we don’t really know why
What are microfilaments?
- Made of actin
- 7nm diameter
- Can be modified by lots of bacteria.
- Salmonella, E coli, shigella, listeria, yersinia and clostridium.
What are the 2 main methods of bacterial entry into cells?
- Trigger method eg salmonella
- Zipper method eg listeria
What is the common thing between the trigger and zipper method of entry?
- They involve rearrangements of the actin cytoskeleton.
- This is controlled by Rho GTPases and inositol phosphate metabolism.
What is the trigger method of bacterial entry?
- Bacteria use a type 3 secretion system to transfer proteins into the host cell.
- These proteins trigger cellular responses that manipulate actin in the cell.
- This causes large membrane ruffles that then take up the bacteria.
What is the zipper method of bacterial entry?
- Adhesion molecule and host receptor interactions trigger proteins in the host cell to change.
- This alters the cytoskeleton to change and take up the bacteria.
- InL A interacts with E-cadherin.
- InL B interacts with the Met receptor which recruits adaptor proteins to interact with actin and phosphatidylinositol .
How does salmonella enter host cells?
- Salmonella is a good regulator of the cytoskeleton.
- It changes the cell by manipulating actin.
- Formation of membrane ruffles happens really quickly. About 20-40 secs
What is the main regulator of the actin cytoskeleton?
Rho GTPases
What are the 3 main Rho GTPases?
- Rho
- Rac
- Cdc42
What does constitutive expression of the 3 Rho GTPases cause?
Rho - stress fibres
Rac - Lamellopodia
Cdc42 - Filopodia
What family does Rho GTPases belong to?
The Ras superfamily
How are Rho GTPases regulated?
- They are active when bound to GTP.
- They are inactive when bound to GDP.
- Guanine nucleotide exchange factors (GEFs) exchange GDP for GTP to activate Rho.
- GTPase-activating proteins (GAPs) hydrolyse GTP to GDP to inactivate Rho.
How can bacteria manipulate Rho GTPase activity?
- They can have mimics of GEFs and GAPs.
- They can have proteins that regulate host GEFs and GAPs
What bacterial proteins mimic GEFs to activate Rho GTPase activity?
- Salmonella SopE/SopE2
- Burkholderia pseudomallei BopE.
- Enteropathogenic E coli Map
- Shigella IpgB1/IpgB2
What bacterial proteins mimic GAPs to deactivate Rho GTPase activity?
- Salmonella SptP
- Yersinia YopE
- Pseudomonas Exo T and Exo S.
Why are bacterial GAP mimics important?
- They are important so the bacteria doesn’t overstimulate the host cell
- This promotes survival
How does salmonella manipulate Rho GTPases and actin for infection?
- Salmonella is reliant on actin rearrangement for infection.
- SopE and SopE2 are GEFs that activate Rac1 and Cdc42.
- This induces lamellipodia and filopodia.
- It also secrets SptP to switch off the Rho GTPases.
What is a secondary function of salmonella’s SopE2?
- It can make host cells less susceptible to further invasion.
- It helps salmonella create its own niche and keep other bacteria out.
What other ways can bacteria regulate Rho GTPases?
- Mostly through post translational modifications.
- ADP-ribosylation, glucosylation, deamination and proteolysis.
- These can switch on or off Rho GTPases.
What are some examples of other regulators of Rho GTPases?
- ADP-ribosylation by clostridium, bacillus and S. aureus.
- Glucosylation by C. diff toxins A and B.
- Deamination/ transglutamination by E coli and bordetella.
- Proteolysis by Yersinia.