Calcium enhances bile salt-dependent virulence activation in Vibrio cholerae

TitleCalcium enhances bile salt-dependent virulence activation in Vibrio cholerae
Publication TypeJournal Article
Year of Publication2017
AuthorsHay A.J, Yang MH, Xia X.Y, Liu Z, Hammons J., Fenical W, Zhu J
JournalInfection and Immunity
Volume85
Date Published2017/01
Type of ArticleArticle
ISBN Number0019-9567
Accession NumberWOS:000394607700009
Keywordsbile salts; Biofilms; calcium; Colonization; dimerization; escherichia-coli; fatty-acids; gene-expression; pathogenesis; plasma-membrane; solubility; tcpp; toxt activity; Vibrio cholerae; virulence gene expression; virulence regulation
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.

DOI10.1128/iai.00707-16
Student Publication: 
No