title: Calcium Enhances Bile Salt-Dependent Virulence Activation in Vibrio cholerae.
abstract: Vibrio cholerae is the causative bacteria of the diarrheal disease cholera, but it also persists in aquatic environments, where it displays an expression profile that is distinct from that during infection. Upon entry into the host, a tightly regulated circuit coordinates the induction of two major virulence factors: cholera toxin and a toxin-coregulated pilus (TCP). It has been shown that a set of bile salts, including taurocholate, serve as host signals to activate V. cholerae virulence through inducing the activity of the transmembrane virulence regulator TcpP. In this study, we investigated the role of calcium, an abundant mental ion in the gut, in the regulation of virulence. We show that whereas Ca2+alone does not affect virulence, Ca2+enhances bile salt-dependent virulence activation for V. cholerae The induction of TCP by murine intestinal contents is counteracted when Ca2+is depleted by the high-affinity calcium chelator EGTA, suggesting that the calcium present in the gut is a relevant signal for V. cholerae virulence induction in vivo We further show that Ca2+enhances virulence by promoting bile salt-induced TcpP-TcpP interaction. Moreover, fluorescence recovery after photobleaching (FRAP) analysis demonstrated that exposure to bile salts and Ca2+together decreases the recovery rate for fluorescently labeled TcpP, but not for another inner membrane protein (TatA). Together, these data support a model in which physiological levels of Ca2+may result in altered bile salt-induced TcpP protein movement and activity, ultimately leading to an increased expression of virulence.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hay
authors.affiliation: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, Hangzhou, Zhejiang, China.
authors.forename: Menghua
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Biotechnology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hammons
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Fenical
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA junzhu@mail.med.upenn.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002771:Cholera / Q000378:metabolism* / Q000382:microbiology*; D002772:Cholera Toxin / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008565:Membrane Proteins; D051379:Mice; D013656:Taurocholic Acid / Q000378:metabolism; D014734:Vibrio cholerae / Q000378:metabolism*; D014774:Virulence / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D008565:Membrane Proteins; D013656:Taurocholic Acid; D002772:Cholera Toxin; D002118:Calcium
keywords: TcpP; Vibrio cholerae; bile salts; calcium; dimerization; virulence gene expression; virulence regulation