Genetic Diversity of Toxigenic and Nontoxigenic Vibrio cholerae Serogroups O1 and O139 Revealed by Array-Based Comparative Genomic Hybridization

Abstract

Toxigenic serogroups O1 and O139 of Vibrio cholerae may cause cholera epidemics or pandemics. Nontoxigenic strains within these serogroups also exist in the environment, and also some may cause sporadic cases of disease. Herein, we investigate the genomic diversity among toxigenic and nontoxigenic O1 and O139 strains by comparative genomic microarray hybridization with the genome of El Tor strain N16961 as a base. Conservation of the toxigenic O1 El Tor and O139 strains is found as previously reported, whereas accumulation of genome changes was documented in toxigenic El Tor strains isolated within the 40 years of the seventh pandemic. High phylogenetic diversity in nontoxigenic O1 and O139 strains is observed, and most of the genes absent from nontoxigenic strains are clustered together in the N16961 genome. By comparing these toxigenic and nontoxigenic strains, we observed that the small chromosome of V. cholerae is quite conservative and stable, outside of the superintegron region. In contrast to the general stability of the genome, the superintegron demonstrates pronounced divergence among toxigenic and nontoxigenic strains. Additionally, sequence variation in virulence-related genes is found in nontoxigenic El Tor strains, and we speculate that these intermediate strains may have pathogenic potential should they acquire CTX prophage alleles and other gene clusters. This genome-wide comparison of toxigenic and nontoxigenic V. cholerae strains may promote understanding of clonal differentiation of V. cholerae and contribute to an understanding of the origins and clonal selection of epidemic strains.

Genomic Science in Understanding Cholera Outbreaks and Evolution of Vibrio cholerae as a Human Pathogen

“…Given that the environment is dominated by non-O1/non-O139 strains, this observation suggests that these virulence factors probably do not promote fitness in the aquatic niche although there is some data that challenges this conclusion for at least chitin binding lectins (Kirn et al 2005). Various typing methods and deep sequencing has enabled more sensitive surveillance of CTX–ϕ in strains isolated from the environment (Rivera et al 2001; Singh et al 2001; Pang et al 2007; Awasthi et al 2012; Hasan et al 2012; Sealfon et al 2012; Sellek et al 2012). The prevalent assumption that the presence of toxigenic strains in water provides proof that toxigenic strain occupy a stable environmental niche needs to be readdressed with modern methods that might differentiate between contamination of the environment by nearby cholera victims as opposed to these strains maintaining themselves within the environment in the absence of infected humans.…”

Detection of toxigenic Vibrio cholerae with new multiplex PCR

“…Cholera is one of the most serious diarrheal diseases, the epidemic form of which is caused by Vibrio cholerae O1 or O139 serogroups [1]. Among the virulence factors of V. cholerae, cholera toxin and toxin-coregulated pilus, encoded by the ctxAB and tcpA genes, respectively, play primary roles in pathogenesis [2,3].…”

Identifications of pathogens—a bioinformatic point of view

“…Finally, there is always the chance that yet unknown variant sequences exist that will escape molecular detection because of mutations. The last case applies to clones that become pathogenic only after acquisition of pathogenicity genes [32,33 ,34 ] or when pathogenicity depends upon the genetic content, that is, by differential regulation of some genes or integration of genes (or domains) that belong to the species or genus gene pool but are not always present in a particular clone [35,36]. In such cases, targeting pathogenicity genes is the best choice, with difficulties similar to housekeeping genes.…”