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

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

Autor Klapproth, Jan Michel A Google Scholar
Sasaki, Maiko Google Scholar
Sherman, Melaine Google Scholar
Babbin, Brian Google Scholar
Donnenberg, Michael S. Google Scholar
Fernandes, Paula J. Google Scholar
Scaletsky, Isabel CA Autor UNIFESP Google Scholar
Kalman, Daniel Google Scholar
Nusrat, Asma Google Scholar
Williams, Ifor R. Google Scholar
Instituição Emory Univ
Univ Maryland
Universidade Federal de São Paulo (UNIFESP)
Resumo Previously, 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.
Idioma Inglês
Data de publicação 2005-03-01
Publicado em Infection and Immunity. Washington: Amer Soc Microbiology, v. 73, n. 3, p. 1441-1451, 2005.
ISSN 0019-9567 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Microbiology
Extensão 1441-1451
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000227373300020
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