Abstract:
:Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5alpha, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Hart E,Yang J,Tauschek M,Kelly M,Wakefield MJ,Frankel G,Hartland EL,Robins-Browne RMdoi
10.1128/IAI.00770-08subject
Has Abstractpub_date
2008-11-01 00:00:00pages
5247-56issue
11eissn
0019-9567issn
1098-5522pii
IAI.00770-08journal_volume
76pub_type
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Infection and immunity
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更新日期:1979-04-01 00:00:00
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