 |
 |
Pathogenic Salmonella enter cells such as those of the intestinal epithelium by altering cellular cytoskeletal structure and inducing membrane ruffling of the infected cell. Salmonella is able to alter the cytoskeleton and membrane through the action of secreted bacterial Sip proteins, SopE, SopB, and SptP that are inserted into the cytosol of the infected cell. Sip proteins encoded by Salmonella are required for the action of SopE and for the invasion of epithelial cells. SipA stabilizes actin filaments, inducing membrane ruffling and perhaps focusing membrane changes where bacteria are localized to allow their entry. SipC produces a similar effect on actin filaments and cytoskeletal structure. SopE acts as an exchange factor on Rac1 and Cdc42, two GTPases in the Rho family that regulate actin cytoskeleton. The activation of Rac2 and Cdc42 by Salmonella SopE induces changes in cytoskeleton structure that allow bacterial entry into the cell. SopB is another salmonella protein that acts as an inositol polyphosphate phosphatase and also stimulates Cdc42 and Rac1. One of the cellular targets of both Cdc42 and Rac1 that affects actin structure is the Arp2/3 complex. Cdc42 and Rac1 activate Wasp, which activates Arp2/3. Activated Arp2/3 induces the formation of actin Y branches, which in combination with changes in actin caused by SipA and SipC help to form lamellipodia, and causes membrane ruffling, leading to entry of Salmonella into the affected cell.
After the initial infection, cells quickly return to their normal morphology, a process that depends on the action of the bacterial protein SptP. While SopE acts as an exchange factor, SptP acts as a GTPase activating protein to inactivate Rac1 and Cdc42 once again. This inactivation of the original entry mechanism provides an example of the delicate balance between infectious organisms and their host. |
|
|
 |
|
|
|
|
 |
|
|
|
|
 |
|
Fu,Y., Galan, J.E. (1999) A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401(6750), 293-7
Galan JE, Zhou D. Striking a balance: modulation of the actin cytoskeleton by Salmonella. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8754-61.
Hardt, W.D. et al. (1998) S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93(5), 815-26
Hayward RD, Koronakiss V. Direct modulation of the host cell cytoskeleton by Salmonella actin-binding proteins. Trends Cell Biol. 2002 Jan;12(1):15-20.
McGhie EJ, Hayward RD, Koronakis V. Cooperation between actin-binding proteins of invasive Salmonella: SipA potentiates SipC nucleation and bundling of actin. EMBO J. 2001 May 1;20(9):2131-9.
Wood, M.W. et al. (1996) SopE, a secreted protein of Salmonella dublin, is translocated into the target eukaryotic cell via a sip-dependent mechanism and promotes bacterial entry. Mol Microbiol 22(2), 327-38
Zhou D, Mooseker MS, Galan JE. An invasion-associated Salmonella protein modulates the actin-bundling activity of plastin. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10176-81.
Zhou, D., Mooseker, M.S., Galan, J.E. (1999) Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283(5410), 2092-5
|
|
|
|
