Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium

Citrobacter rodentium is used as an in vivo model system for clinically significant enteric pathogens such as enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). These pathogens all colonize the lumen side of the host gastrointestinal tract via attaching and effacing (A/E...

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Autor principal: Simmons, Cameron
Formato: Journal Article
Lenguaje:inglés
Publicado: 2018
Acceso en línea:https://demo7.dspace.org/handle/123456789/213
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author Simmons, Cameron
author_browse Simmons, Cameron
author_facet Simmons, Cameron
author_sort Simmons, Cameron
collection DSpace
description Citrobacter rodentium is used as an in vivo model system for clinically significant enteric pathogens such as enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). These pathogens all colonize the lumen side of the host gastrointestinal tract via attaching and effacing (A/E) lesion formation. In order to identify genes required for the colonization of A/E-forming pathogens, a library of signature-tagged transposon mutants of C. rodentium was constructed and screened in mice. Of the 576 mutants tested, 14 were attenuated in their ability to colonize the descending colon. Of these, eight mapped to the locus of enterocyte effacement (LEE), which is required for the formation of A/E lesions, underlying the importance of this mechanism for pathogenesis. Another mutant, P5H2, was found to have a transposon insertion in an open reading frame that has strong similarity to type IV pilus nucleotide-binding proteins. The region flanking the transposon insertion was sequenced, identifying a cluster of 12 genes that encode the first described pilus of C. rodentium (named colonization factor Citrobacter, CFC). The proteins encoded by cfc genes have identity to proteins of the type IV COF pilus of enterotoxigenic E. coli (ETEC), the toxin co-regulated pilus of Vibrio cholerae and the bundle-forming pilus of EPEC. A non-polar mutation in cfcI, complementation of this strain with wild-type cfcI and complementation of strain P5H2 with wild-type cfcH confirmed that these genes are required for colonization of the gastrointestinal tract by C. rodentium. Thus, CFC provides a convenient model to study type IV pilus-mediated pathogen-host interactions under physiological conditions in the natural colonic environment.
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spelling oai:localhost:123456789-2132021-04-07T16:30:08Z Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium Simmons, Cameron Citrobacter rodentium is used as an in vivo model system for clinically significant enteric pathogens such as enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). These pathogens all colonize the lumen side of the host gastrointestinal tract via attaching and effacing (A/E) lesion formation. In order to identify genes required for the colonization of A/E-forming pathogens, a library of signature-tagged transposon mutants of C. rodentium was constructed and screened in mice. Of the 576 mutants tested, 14 were attenuated in their ability to colonize the descending colon. Of these, eight mapped to the locus of enterocyte effacement (LEE), which is required for the formation of A/E lesions, underlying the importance of this mechanism for pathogenesis. Another mutant, P5H2, was found to have a transposon insertion in an open reading frame that has strong similarity to type IV pilus nucleotide-binding proteins. The region flanking the transposon insertion was sequenced, identifying a cluster of 12 genes that encode the first described pilus of C. rodentium (named colonization factor Citrobacter, CFC). The proteins encoded by cfc genes have identity to proteins of the type IV COF pilus of enterotoxigenic E. coli (ETEC), the toxin co-regulated pilus of Vibrio cholerae and the bundle-forming pilus of EPEC. A non-polar mutation in cfcI, complementation of this strain with wild-type cfcI and complementation of strain P5H2 with wild-type cfcH confirmed that these genes are required for colonization of the gastrointestinal tract by C. rodentium. Thus, CFC provides a convenient model to study type IV pilus-mediated pathogen-host interactions under physiological conditions in the natural colonic environment. 2018-09-14T11:15:08Z 2017-07-05T05:22:57Z 2018-09-14T11:15:08Z 2003-05-01 Journal Article https://demo7.dspace.org/handle/123456789/213 English
spellingShingle Simmons, Cameron
Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium
title Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium
title_full Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium
title_fullStr Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium
title_full_unstemmed Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium
title_short Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium
title_sort identification of a novel type iv pilus gene cluster required for gastrointestinal colonization of citrobacter rodentium
url https://demo7.dspace.org/handle/123456789/213
work_keys_str_mv AT simmonscameron identificationofanoveltypeivpilusgeneclusterrequiredforgastrointestinalcolonizationofcitrobacterrodentium