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dc.contributor.authorAl-Hasani, Keith
dc.contributor.authorNavarro-Garcia, Fernando
dc.contributor.authorHuerta, Jazmin
dc.contributor.authorSakellaris, Harry
dc.contributor.authorAdler, Ben
dc.date.accessioned2017-05-03T12:44:47Z
dc.date.available2017-05-03T12:44:47Z
dc.date.issued2009
dc.date.modified2014-07-28T06:49:33Z
dc.identifier.issn19326203
dc.identifier.doi10.1371/journal.pone.0008223
dc.identifier.urihttp://hdl.handle.net/10072/61390
dc.description.abstractBackground We have previously shown that the enterotoxin SigA which resides on the she pathogenicity island (PAI) of S. flexneri 2a is an autonomously secreted serine protease capable of degrading casein. We have also demonstrated that SigA is cytopathic for HEp-2 cells and plays a role in the intestinal fluid accumulation associated with S. flexneri infections. Methods/Principal Findings In this work we show that SigA binds specifically to HEp-2 cells and degrades recombinant human aII spectrin (a-fodrin) in vitro, suggesting that the cytotoxic and enterotoxic effects mediated by SigA are likely associated with the degradation of epithelial fodrin. Consistent with our data, this study also demonstrates that SigA cleaves intracellular fodrin in situ, causing its redistribution within cells. These results strongly implicate SigA in altering the cytoskeleton during the pathogenesis of shigellosis. On the basis of these findings, cleavage of fodrin is a novel mechanism of cellular intoxication for a Shigella toxin. Furthermore, information regarding immunogenicity to SigA in infected patients is lacking. We studied the immune response of SigA from day 28 post-challenge serum of one volunteer from S. flexneri 2a challenge studies. Our results demonstrate that SigA is immunogenic following infection with S. flexneri 2a. Conclusions This work shows that SigA binds to epithelial HEp-2 cells as well as being able to induce fodrin degradation in vitro and in situ, further extending its documented role in the pathogenesis of Shigella infections.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent749642 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome8223-1
dc.relation.ispartofpagetoe8223-5
dc.relation.ispartofissue12
dc.relation.ispartofjournalPL o S One
dc.relation.ispartofvolume4
dc.rights.retentionY
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchcode060599
dc.titleThe Immunogenic SigA Enterotoxin of Shigella flexneri 2a Binds to HEp-2 Cells and Induces Fodrin Redistribution in Intoxicated Epithelial Cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://www.plos.org/journals/license.html
gro.rights.copyright© 2009 Al-Hasani et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorSakellaris, Harry


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