Crossref journal-article
American Society for Microbiology
Infection and Immunity (235)
Abstract

ABSTRACTShigella flexneriis a gram-negative, facultative intracellular pathogen that invades the colonic epithelium and causes bacillary dysentery. We previously demonstrated thatS. flexneriinhibits staurosporine-induced apoptosis in infected epithelial cells and that a ΔmxiEmutant is unable to inhibit apoptosis. Therefore, we hypothesized that an MxiE-regulated gene was responsible for protection of epithelial cells from apoptosis. Analysis of all MxiE-regulated genes yielded no mutants that lacked the ability to prevent apoptosis. Spa15, which is defined as a type III secretion system chaperone, was analyzed since it associates with MxiE. A Δspa15mutant was unable to prevent staurosporine-induced apoptosis. C-terminal hemagglutinin-taggedspa15was secreted byS. flexneriwithin 2 h in the Congo red secretion assay, and secretion was dependent on the type III secretion system. Spa15 was also secreted byShigellain infected epithelial cells, as verified by immunofluorescence analysis. Spa15 secretion was decreased in the ΔmxiEmutant, which demonstrates why this mutant is unable to prevent staurosporine-induced apoptosis. Our data are the first to show that Spa15 is secreted in a type III secretion system-dependent fashion, and the absence of Spa15 in the Δspa15mutant results in the loss of protection from staurosporine-induced apoptosis in epithelial cells. Thus, Spa15 contributes to the intracellular survival ofShigellaby blocking apoptosis in the infected host cell.

Bibliography

Faherty, C. S., & Maurelli, A. T. (2009). Spa15 ofShigella flexneriIs Secreted through the Type III Secretion System and Prevents Staurosporine-Induced Apoptosis. Infection and Immunity, 77(12), 5281–5290.

Authors 2
  1. Christina S. Faherty (first)
  2. Anthony T. Maurelli (additional)
References 47 Referenced 32
  1. 10.1128/IAI.67.11.6056-6066.1999
  2. 10.1016/S0278-5846(03)00016-2
  3. Ashida, H., T. Toyotome, T. Nagai, and C. Sasakawa. 2007. Shigella chromosomal IpaH proteins are secreted via the type III secretion system and act as effectors. Mol. Microbiol.63:680-693. (10.1111/j.1365-2958.2006.05547.x) / Mol. Microbiol. (2007)
  4. 10.1128/iai.65.10.4005-4010.1997
  5. 10.1073/pnas.86.10.3867
  6. 10.1046/j.1365-2958.2000.02179.x
  7. 10.1128/IAI.01866-06
  8. 10.1006/jmcc.1998.0851
  9. 10.4049/jimmunol.180.10.6816
  10. 10.1073/pnas.120163297
  11. 10.1016/j.ceb.2005.09.001
  12. 10.1093/humrep/deh806
  13. 10.1128/jb.75.5.604-610.1958
  14. 10.1128/MMBR.68.4.771-795.2004
  15. 10.1152/ajpgi.00350.2003
  16. 10.1016/j.micinf.2007.11.011
  17. 10.1016/S0022-2836(83)80284-8
  18. 10.1128/iai.57.10.2963-2970.1989
  19. 10.1016/j.femsre.2003.07.002
  20. 10.1128/IAI.72.7.3951-3960.2004
  21. 10.1172/JCI117676
  22. 10.1128/JB.184.16.4409-4419.2002
  23. 10.4049/jimmunol.175.3.1735
  24. 10.1099/mic.0.27639-0
  25. 10.1083/jcb.150.6.1479
  26. 10.1016/j.molcel.2006.01.026
  27. 10.1128/iai.49.1.164-171.1985
  28. 10.1128/JB.184.24.6751-6759.2002
  29. 10.1128/IAI.66.9.4237-4243.1998
  30. 10.1016/0092-8674(94)90260-7
  31. 10.1128/iai.56.11.2933-2941.1988
  32. 10.1128/iai.48.1.124-129.1985
  33. 10.1074/jbc.M502509200
  34. 10.1046/j.1365-2958.2002.02835.x
  35. 10.1111/j.1365-2958.2005.04645.x
  36. 10.1128/JB.01824-07
  37. 10.1128/IAI.70.6.3199-3207.2002
  38. 10.1128/iai.64.7.2752-2764.1996
  39. 10.1128/CMR.00032-07
  40. 10.1093/emboj/19.15.3876
  41. 10.1074/jbc.M101882200
  42. 10.1093/emboj/16.10.2717
  43. 10.1128/jb.174.6.1990-2001.1992
  44. Wright, K., G. Kolios, J. Westwick, and S. G. Ward. 1999. Cytokine-induced apoptosis in epithelial HT-29 cells is independent of nitric oxide formation. Evidence for an interleukin-13-driven phosphatidylinositol 3-kinase-dependent survival mechanism. J. Biol. Chem.274:17193-17201. / Evidence for an interleukin-13-driven phosphatidylinositol 3-kinase-dependent survival mechanism. J. Biol. Chem. (1999)
  45. 10.1096/fj.05-4226com
  46. 10.1128/IAI.00594-06
  47. 10.1128/iai.64.12.5357-5365.1996
Dates
Type When
Created 15 years, 10 months ago (Oct. 5, 2009, 9:05 p.m.)
Deposited 1 year, 5 months ago (March 16, 2024, 7:16 p.m.)
Indexed 1 month, 3 weeks ago (June 30, 2025, 1:05 a.m.)
Issued 15 years, 8 months ago (Dec. 1, 2009)
Published 15 years, 8 months ago (Dec. 1, 2009)
Published Print 15 years, 8 months ago (Dec. 1, 2009)
Funders 0

None

@article{Faherty_2009, title={Spa15 ofShigella flexneriIs Secreted through the Type III Secretion System and Prevents Staurosporine-Induced Apoptosis}, volume={77}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.00800-09}, DOI={10.1128/iai.00800-09}, number={12}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Faherty, Christina S. and Maurelli, Anthony T.}, year={2009}, month=dec, pages={5281–5290} }