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.
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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) |
@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} }