Interdisciplinary Life Science - PULSe Great research is a matter of choice

Daoguo Zhou

Daoguo Zhou Profile Picture

Associate Professor of Biological Sciences
Ph.D - 1995 - University of Iowa

Contact Info:

Training Group(s):
Immunology and Infectious Diseases
Membrane Biology

Current Research Interests:

Salmonella typhimurium makes a panel of specialized proteins that allows it to invade non-phagocytic intestinal epithelial cells, the first step in the disease process. Previous research has established that upon contact with the intestinal epithelial cells, Salmonella injects a set of proteins into the host cells through the bacterially encoded type III protein secretion system. These proteins subvert host cell signal transduction pathways to induce profuse actin cytoskeletal rearrangements and membrane ruffling, leading to the uptake of the bacterium. This uptake process is a highly regulated event and requires the coordinated action of the injected bacterial proteins as well as host proteins. Studying the interaction between bacteria and their hosts has emerged as one of the most exciting areas of cellular microbiology. It will not only broaden our understanding of bacterial pathogenesis, but also will provide unexpected insights into basic host cellular functions, such as the cytoskeletal rearrangements and signal transduction pathways controlling cell movement.

My laboratory is interested in identifying and characterizing bacterial and host cellular proteins that are involved in Salmonella-induced actin cytoskeletal rearrangements, especially cellular proteins whose activities are modulated by Salmonella proteins. I have recently shown that SipA, a Salmonella protein injected into host cells, binds actin, a host protein with a number of essential activities including a central role in cellular uptake process. Upon binding to actin, SipA modulates the actin dynamics by decreasing the critical concentration for actin polymerization and inhibiting depolymerization of actin filaments, thus facilitating more efficient uptake of the bacteria. In addition, SipA also increases the bundling activity of T-plastin upon binding to actin, which could serve to increase the stability of the actin bundles that drive and support the growth of the membrane ruffles and filopodia that ultimately engulf and internalize the bacteria. Future studies in my laboratory will involve detailed functional characterization of the SipA protein, identification of host cellular proteins engaged by Salmonella, and investigation of the biochemical mechanisms for plastin actin-bundling activity.

Selected Publications:

1. Kim, J. J., D. Zhou, R. E. Mandrell & J. M. Griffiss. (1992) Effect of exogenous sialylation of the lipooligosaccharide of Neisseria gonorrhoeae on opsonophagocytosis. Infect Immun 60: 4439-4442.

2. Stephens, D. S., C. F. McAllister, D. Zhou, F. K. Lee & M. A. Apicella. (1994) Tn916-generated, lipooligosaccharide mutants of Neisseria meningitidis and Neisseria gonorrhoeae. Infect Immun 62: 2947-2952.

3. Zhou, D., N. G. Lee & M. A. Apicella. (1994a) Lipooligosaccharide biosynthesis in Neisseria gonorrhoeae: cloning, identification and characterization of the alpha 1,5 heptosyltransferase I gene (rfaC). Mol Microbiol 14: 609-618.

4. Zhou, D., D. S. Stephens, B. W. Gibson, J. J. Engstrom, C. F. McAllister, F. K. Lee & M. A. Apicella. (1994b) Lipooligosaccharide biosynthesis in pathogenic Neisseria. Cloning, identification, and characterization of the phosphoglucomutase gene. J Biol Chem 269: 11162-11169.

5. Lee, F. K., D. S. Stephens, B. W. Gibson, J. J. Engstrom, D. Zhou & M. A. Apicella. (1995) Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB. Infect Immun 63: 2508-2515.

6. Apicella, M. A., M. Ketterer, F. K. Lee, D. Zhou, P. A. Rice & M. S. Blake. (1996) The pathogenesis of gonococcal urethritis in men: confocal and immunoelectron microscopic analysis of urethral exudates from men infected with Neisseria gonorrhoeae. J Infect Dis 173: 636-646.

7. Zhou, D. & M. A. Apicella. (1996) Plasmids with erythromycin resistance and catechol 2,3-dioxygenase- or beta-galactosidase-encoding gene cassettes for use in Neisseria spp. Gene 171: 133-134.

8. Estabrook, M. M., D. Zhou & M. A. Apicella. (1998) Nonopsonic phagocytosis of group C Neisseria meningitidis by human neutrophils. Infect Immun 66: 1028-1036.

9. Zhou, D., W. D. Hardt & J. E. Galán. (1999a) Salmonella typhimurium encodes a putative iron transport system within the centisome 63 pathogenicity island. Infect Immun 67: 1974-1981.

10. Zhou, D., M. S. Mooseker & J. E. Galán. (1999b) An invasion-associated Salmonella protein modulates the actin-bundling activity of plastin. Proc Natl Acad Sci U S A 96: 10176-10181.

11. Zhou, D., M. S. Mooseker & J. E. Galán. (1999c) Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283: 2092-2095.

12. Galán, J. E. & D. Zhou. (2000) Striking a balance: Modulation of the actin cytoskeleton by Salmonella. Proc Natl Acad Sci U S A 97: 8754-8761.

13. Mitra, K., D. Zhou & J. E. Galán. (2000) Biophysical characterization of SipA, an actin-binding protein from Salmonella enterica. FEBS Lett 482: 81-84.

14. Zhou, D. (2001) Collective efforts to modulate the host actin cytoskeleton by Salmonella type III-secreted effector proteins. Trends Microbiol 9: 567-569.

15. Zhou, D., L. M. Chen, L. Hernandez, S. B. Shears & J. E. Galán. (2001) A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol Microbiol 39: 248-259.

16. Zhou, D. & J. E. Galán. (2001) Salmonella entry into host cells: the work in concert of type III secreted effector proteins. Microbes Infect 3: 1293-1298.

17. Galkin, V. E., A. Orlova, M. S. VanLoock, D. Zhou, J. E. Galán & E. H. Egelman. (2002) The bacterial protein SipA polymerizes G-actin and mimics muscle nebulin. Nat Struct Biol 9: 518-521.

18. Higashide, W., S. Dai, V. P. Hombs & D. Zhou. (2002) Involvement of SipA in modulating actin dynamics during Salmonella invasion into cultured epithelial cells. Cell Microbiol 4: 357-365.

19. Dai, S., P. D. Sarmiere, O. Wiggan, J. R. Bamburg & D. Zhou. (2004) Efficient Salmonella entry requires activity cycles of host ADF and cofilin. Cell Microbiol 6: 459-471.

20. Dai, S. & D. Zhou. (2004) Secretion and function of Salmonella SPI-2 effector SseF require its chaperone, SscB. J Bacteriol 186: 5078-5086.

21. Zhou, D. (2004) Bacterial invasion into non-phagocytic cells. In: Molecular Paradigms of Infectious Disease. C. A. Nickerson & M. J. Schurr (eds). Springer Ecience+Business Media, LLC, pp. 247-273.

22. Chang, J., J. Chen & D. Zhou. (2005) Delineation and characterization of the actin nucleation and effector translocation activities of Salmonella SipC. Mol Microbiol 55: 1379 - 1389.

23. Zhang, Y., W. Higashide, S. Dai, D. M. Sherman & D. Zhou. (2005) Recognition and ubiquitination of Salmonella type III effector SopA by a ubiquitin E3 ligase, HsRMA1. J Biol Chem 280: 38682-38688.

24. Higashide, W. & D. Zhou. (2006) The first 45 amino acids of SopA are necessary for InvB binding and SPI-1 secretion. J Bacteriol 188: 2411-2420.

25. Hu, H., Q. Sa, T. M. Koehler, A. I. Aronson & D. Zhou. (2006) Inactivation of Bacillus anthracis spores in murine primary macrophages. Cell Microbiol 8: 1634-1642.

26. Zhang, Y., W. M. Higashide, B. A. McCormick, J. Chen & D. Zhou. (2006) The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase. Mol Microbiol 62: 786-793.

27. Zuo, X., J. Zhang, Y. Zhang, S. C. Hsu, D. Zhou & W. Guo. (2006) Exo70 interacts with the Arp2/3 complex and regulates cell migration. Nat Cell Biol 8: 1383-1388.

28. Chang, J., S. K. Myeni, T. L. Lin, C. C. Wu, C. J. Staiger & D. Zhou. (2007) SipC multimerization promotes actin nucleation and contributes to Salmonella-induced inflammation. Mol Microbiol 66: 1548–1556.

29. Dai, S., Y. Zhang, T. Weimbs, M. B. Yaffe & D. Zhou. (2007) Bacteria-generated PtdIns(3)P recruits VAMP8 to facilitate phagocytosis. Traffic 8: 1365-1374.

30. Diao, J., Y. Zhang, J. M. Huibregtse, D. Zhou & J. Chen. (2008) Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. Nat Struct Mol Biol 15: 65-70.

31. Wang, X. & D. Zhou. (2009) Salmonella Invasion. J Microbes Infect 4: 124-128.

32. Myeni, S. K. & D. Zhou. (2010) The C-terminus of SipC binds and bundles F-actin to promote Salmonella invasion. J Biol Chem In Press.

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