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Infection and Immunity, December 2009, p. 5281-5290, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00800-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Spa15 of Shigella flexneri Is Secreted through the Type III Secretion System and Prevents Staurosporine-Induced Apoptosis{triangledown}

Christina S. Faherty and Anthony T. Maurelli*

Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799

Received 16 July 2009/ Returned for modification 13 August 2009/ Accepted 22 September 2009

Shigella flexneri is a gram-negative, facultative intracellular pathogen that invades the colonic epithelium and causes bacillary dysentery. We previously demonstrated that S. flexneri inhibits staurosporine-induced apoptosis in infected epithelial cells and that a {Delta}mxiE mutant 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 {Delta}spa15 mutant was unable to prevent staurosporine-induced apoptosis. C-terminal hemagglutinin-tagged spa15 was secreted by S. flexneri within 2 h in the Congo red secretion assay, and secretion was dependent on the type III secretion system. Spa15 was also secreted by Shigella in infected epithelial cells, as verified by immunofluorescence analysis. Spa15 secretion was decreased in the {Delta}mxiE mutant, 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 {Delta}spa15 mutant results in the loss of protection from staurosporine-induced apoptosis in epithelial cells. Thus, Spa15 contributes to the intracellular survival of Shigella by blocking apoptosis in the infected host cell.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799. Phone: (301) 295-3415. E-mail: amaurelli{at}usuhs.mil

{triangledown} Published ahead of print on 5 October 2009.

Editor: S. M. Payne

Infection and Immunity, December 2009, p. 5281-5290, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00800-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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