title: Coordinated regulation of virulence by quorum sensing and motility pathways during the initial stages of Vibrio cholerae infection.
abstract: Pathogenic bacteria, such as Vibrio cholerae, must be capable of adapting to diverse living conditions, especially when transitioning from life in environmental reservoirs to life in a host. The abilities to sense arrival at a site suitable for colonization or infection and to respond with appropriate alterations in gene expression are crucial for a pathogen's success. Recently, we have shown that V. cholerae is able to recognize that it has reached its colonization site in the small intestine by sensing breakage of its flagellum as it penetrates the mucosal layer overlaying the intestinal epithelium. Flagellar loss results in the release of the anti-sigma factor FlgM and subsequent activation of the alternative sigma-factor FliA. FliA represses the quorum sensing-controlled transcriptional regulator, HapR, allowing increased expression of virulence factors such as Cholera Toxin (CT) and the Toxin Coregulated Pilus (TCP). In this way, the de-repression of virulence factor expression coincides with the arrival of bacteria at the site of infection at the intestinal mucosa. Our work reveals an interesting interplay between motility and quorum sensing signaling pathways to precisely time virulence gene expression during colonization.
authors.affiliation: Department of Microbiology; University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Tsou
authors.forename: Erin M
authors.initials: EM
authors.lastname: Frey
authors.forename: Ansel
authors.initials: A
authors.lastname: Hsiao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
references.citation: J Bacteriol. 1994 Jan;176(2):269-75
references.pmid: 8288518
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14542-7
references.pmid: 16983078
references.citation: PLoS Pathog. 2006 Oct;2(10):e109
references.pmid: 17054394
references.citation: Annu Rev Cell Dev Biol. 2005;21:319-46
references.pmid: 16212498
references.citation: Cell. 2004 Jul 9;118(1):69-82
references.pmid: 15242645
references.citation: Mol Microbiol. 2002 Nov;46(4):1135-47
references.pmid: 12421317
references.citation: Infect Immun. 2007 Jan;75(1):122-6
references.pmid: 17074850
references.citation: Curr Issues Intest Microbiol. 2002 Sep;3(2):29-38
references.pmid: 12400636
references.citation: Genes Dev. 2008 Jan 15;22(2):226-38
references.pmid: 18198339
references.citation: Infect Immun. 2007 Dec;75(12):5542-9
references.pmid: 17875629
references.citation: Mol Microbiol. 1999 Feb;31(3):763-71
references.pmid: 10048021
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9769-74
references.pmid: 18606988
references.citation: Science. 1993 Nov 19;262(5137):1277-80
references.pmid: 8235660
references.citation: FEMS Microbiol Rev. 2001 Aug;25(4):365-404
references.pmid: 11524130
references.citation: Dev Cell. 2003 Oct;5(4):647-56
references.pmid: 14536065
references.citation: Nature. 2007 Dec 6;450(7171):883-6
references.pmid: 18004304
references.citation: Microbiol Mol Biol Rev. 1998 Dec;62(4):1301-14
references.pmid: 9841673
references.citation: Cell. 2002 Aug 9;110(3):303-14
references.pmid: 12176318
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3129-34
references.pmid: 11854465