Citrobacter rodentium lifA/efa1 is essential for colonic colonization and crypt cell hyperplasia in vivo

dc.contributor.authorKlapproth, Jan Michel A
dc.contributor.authorSasaki, Maiko
dc.contributor.authorSherman, Melaine
dc.contributor.authorBabbin, Brian
dc.contributor.authorDonnenberg, Michael S.
dc.contributor.authorFernandes, Paula J.
dc.contributor.authorScaletsky, Isabel CA [UNIFESP]
dc.contributor.authorKalman, Daniel
dc.contributor.authorNusrat, Asma
dc.contributor.authorWilliams, Ifor R.
dc.contributor.institutionEmory Univ
dc.contributor.institutionUniv Maryland
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:37:41Z
dc.date.available2016-01-24T12:37:41Z
dc.date.issued2005-03-01
dc.description.abstractPreviously, we have identified a large gene (lifA, for lymphocyte inhibitory factor A) in enteropathogenic Escherichia coli (EPEC) encoding a protein termed lymphostatin that suppresses cytokine expression in vitro. This protein also functions as an adhesion factor for enterohemorrhagic E. coli (EHEC) and Shiga toxin-producing E. coli and is alternatively known as efa1 (EHEC factor for adherence 1). the lifA/efa1 gene is also present in Citrobacter rodentium, an enteric pathogen that causes a disease termed transmissible murine colonic hyperplasia (TMCH), which induces colitis and massive crypt cell proliferation, in mice. To determine if lifA/efa1 is required for C. rodentium-induced colonic pathology in vivo, three in-frame mutations were generated, disrupting the glycosyltransferase (GIM12) and protease (PrMC31) motifs and a domain in between that does not encode any known activity (EID3). in contrast to infection with wild-type C. rodentium, that with any of the lifA/efa1 mutant strains did not induce weight loss or TMCH. Enteric infection with motif mutants GIM12 and PrM31 resulted in significantly reduced colonization counts during the entire 20-day course of infection. in contrast, EID3 was indistinguishable from the wild type during the initial colonic colonization, but cleared rapidly after day 8 of the infection. the colonic epithelium of all infected mice displayed increased epithelial regeneration. However, significantly increased regeneration was observed by day 20 only in mice infected with the wild-type in comparison to those infected with lifA/efa1 mutant EID3. in summary, lifA/efa1 is a critical gene outside the locus for enterocyte effacement that regulates bacterial colonization, crypt cell proliferation, and epithelial cell regeneration.en
dc.description.affiliationEmory Univ, Div Digest Dis, Atlanta, GA 30345 USA
dc.description.affiliationEmory Univ, Dept Pathol, Atlanta, GA 30345 USA
dc.description.affiliationUniv Maryland, Div Infect Dis, Baltimore, MD 21201 USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1441-1451
dc.identifierhttp://dx.doi.org/10.1128/IAI.73.3.1441-1451.2005
dc.identifier.citationInfection and Immunity. Washington: Amer Soc Microbiology, v. 73, n. 3, p. 1441-1451, 2005.
dc.identifier.doi10.1128/IAI.73.3.1441-1451.2005
dc.identifier.fileWOS000227373300020.pdf
dc.identifier.issn0019-9567
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/28165
dc.identifier.wosWOS:000227373300020
dc.language.isoeng
dc.publisherAmer Soc Microbiology
dc.relation.ispartofInfection and Immunity
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleCitrobacter rodentium lifA/efa1 is essential for colonic colonization and crypt cell hyperplasia in vivoen
dc.typeinfo:eu-repo/semantics/article
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