Genomic Diversity of Nontoxigenic Vibrio cholerae O1 Strains Isolated in the Territory of Russia and Neighboring States

Apart from strains of Vibrio cholerae biovar El Tor imported from cholera-endemic regions, causing outbreaks or sporadic cases of cholera, a significant number of different variants of nontoxigenic strains that can induce acute enteric infections are annually isolated from surface water bodies and human beings in the Russian Federation. We have carried out analysis of whole genomes that we sequenced (29) and obtained from the GenBank database (11), of 40 toxigenic and nontoxigenic strains isolated in cholera nonendemic (Russia, Ukraine, Turkmenistan, Georgia) and endemic (India, Bangladesh, Vietnam, and others) territories. It is established that they fall into three main groups which differ in the composition of mobile elements with pathogenicity and epidemicity genes, both from toxigenic isolates and among themselves. Nontoxigenic strains of the first group are deprived of all intact virulence prophages (CTXφ, RS1φ, TLCφ), pathogenicity (VPI-1, VPI-2) and pandemicity (VSP-I, VSP-II) islands, which testifies to their epidemic safety. The strains of the second group differ from the first one by the presence of the TLCφ prophage and two pathogenicity islands. It is demonstrated that this population of nontoxigenic strains, which is detected only in the Russian Federation and other cholera nonendemic regions, does not pose a potential epidemic hazard as was assumed earlier, despite the availability of tcpA–F genes in VPI-1. The lack of not only the CTXφ prophage but also VSP-I and VSP-II, which we revealed in these strains, eliminates the possibility of their reversion to epidemically hazardous ones. The strains of the third group have opulent similarity to toxigenic strains, being different in the absence of the CTXφ prophage only. It is this group of nontoxigenic strains, isolated only in cholera-endemic territories and capable of acquiring CTXφ through phage conversion, that is potentially epidemically hazardous. The results of whole genome SNP analysis of 58 different strains confirmed these data. We have also shown with the help of model animals (7- to 8-day-old rabbits) that nontoxigenic strains, irrespective of the structure of their genome, cannot cause typical cholera infection. The results provide insight into genomic diversity of nontoxigenic strains, as well as draw us nearer to an understanding of the mechanisms of reversion of their different variants into epidemically hazardous isolates.