Effects of Polyamines on Vibrio cholerae Virulence Properties

Abstract

Vibrio cholerae is the causative agent of the severe enteric disease cholera. To cause cholera the bacterium must be able to synthesize both cholera toxin (CT) and toxin-coregulated pilus (TCP) which mediates autoagglutination and is required for colonization of the small intestine. Only a few environmental signals have been shown to regulate V. cholerae virulence gene expression. Polyamines, which are ubiquitous in nature, and have been implicated in regulating virulence gene expression in other bacteria, have not been extensively studied for their effect on V. cholerae virulence properties. The objective of this study was to test the effect of several polyamines that are abundant in the human intestine on V. cholerae virulence properties. All of the polyamines tested inhibited autoagglutination of V. cholerae O1 classical strain in a concentration dependent manner. Putrescine and cadaverine decreased the synthesis of the major pilin subunit, TcpA, spermidine increased its production, and spermine had no effect. Putrescine and spermidine led to a decrease and increase, respectively, on the relative abundance of TCP found on the cell surface. Spermine led to a small reduction in cholera toxin synthesis whereas none of the other polyamines had an effect. The polyamines did not affect pili bundling morphology, but caused a small reduction in CTXφ transduction, indicating that the TCP present on the cell surface may not be fully functional. We hypothesize the inhibition of autoagglutination is likely to be caused by the positively charged amine groups on the polyamines electrostatically disrupting the pili-pili interactions which mediate autoagglutination. Our results implicate that polyamines may have a protective function against colonization of the small intestine by V. cholerae.

A Novel Polyamine Allosteric Site of SpeG from Vibrio cholerae Is Revealed by Its Dodecameric Structure

“…In contrast, Shigella has silenced or deleted speG to increase its pathogenicity and survival in macrophages [2]. Studies have also shown that polyamines such as putrescine, spermidine, and spermine are found in very high concentrations in the human gut and may influence colonization of V. cholerae [11]. Biofilms in V. cholerae are important for its survival, and it has been shown that high concentrations of spermidine can disrupt biofilm formation.…”

“…Although deleting the spermidine import gene potD1 in V. cholerae causes an increase in biofilm formation [12], the role of SpeG may also contribute to reducing spermidine concentrations in the cell. Overall, utilization of SpeG to prevent polyamine toxicity appears to be common for both pathogenic and non-pathogenic bacteria [1, 4, 6, 11]. …”

The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae

“…Excess polyamines are growth inhibitory, which necessitates regulation of their production (He et al, 1993). Cadaverine has also been found to reduce V. cholerae auto-agglutination, probably as a result of its positively charged amine groups electrostatically disrupting the pili interactions (Goforth et al, 2013). Thus, excess cadaverine could hinder intestinal colonization.…”

The ins and outs of cyclic di-GMP signaling in Vibrio cholerae

“…The sensor protein NspS regulates activity of a PDE in response to polyamines. Two structurally-similar polyamines, norspermidine and spermidine, regulate V. cholerae c-di-GMP and biofilm formation [55]. Exogenous norspermidine activates V. cholerae biofilm formation through a pathway involving the membrane-bound PDE MbaA and its periplasmic partner protein NspS, which are encoded in the same operon [56].…”