{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:54:44Z","timestamp":1789991684088,"version":"4.0.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Shigella flexneri<\/jats:italic>\n            is a facultative intracellular organism that causes bacillary dysentery. The\n            <jats:italic>Shigella<\/jats:italic>\n            IpaB protein activates caspase 1 in macrophages, which eventually leads to apoptosis. In contrast, epithelial cells infected with\n            <jats:italic>Shigella<\/jats:italic>\n            undergo a stress response but do not die. Therefore, the objective of this study was to determine if\n            <jats:italic>Shigella<\/jats:italic>\n            has the ability to inhibit apoptosis in epithelial cells. A modified gentamicin protection assay was used to investigate if HeLa cells infected with\n            <jats:italic>S. flexneri<\/jats:italic>\n            are able to resist the induction of apoptosis following treatment with 4 \u03bcM of staurosporine. Nuclear staining and immunofluorescence revealed that infected cells remained healthy while uninfected cells appeared apoptotic. Only uninfected cells had detectable levels of activated caspase 3 upon immunofluorescence, and this was verified by Western blot analysis. Despite interfering with caspase 3 activation,\n            <jats:italic>Shigella<\/jats:italic>\n            -infected cells treated with staurosporine did have cytochrome\n            <jats:italic>c<\/jats:italic>\n            release and caspase 9 activation, indicating that\n            <jats:italic>Shigella<\/jats:italic>\n            protects epithelial cells from apoptosis by inhibiting caspase 3 activation. Analysis of\n            <jats:italic>S. flexneri<\/jats:italic>\n            mutants showed that invasion and a functional type III secretion system were required to block apoptosis. In addition, a mutant with a deletion in\n            <jats:italic>mxiE<\/jats:italic>\n            , which encodes a transcriptional activator for genes induced intracellularly, failed to inhibit apoptosis. Therefore, protection of epithelial cells from apoptosis by\n            <jats:italic>S. flexneri<\/jats:italic>\n            is regulated by one or more of the bacterial genes under the control of\n            <jats:italic>mxiE<\/jats:italic>\n            . We believe that\n            <jats:italic>S. flexneri<\/jats:italic>\n            , like other pathogens, inhibits apoptosis in epithelial cells but causes apoptosis in macrophages to ensure survival inside the host.\n          <\/jats:p>","DOI":"10.1128\/iai.01866-06","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T01:28:43Z","timestamp":1173144523000},"page":"2531-2539","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["<i>Shigella flexneri<\/i>\n            Inhibits Staurosporine-Induced Apoptosis in Epithelial Cells"],"prefix":"10.1128","volume":"75","author":[{"given":"Christina S.","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, F. Edward He\u0301bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Maurelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, F. 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