Genome structure and origin of nontoxigenic strains of <Emphasis Type="Italic">Vibrio cholerae</Emphasis> of El Tor biovar with different epidemiological significance

Intraspecies genetic differentiation of nontoxigenic strains of Vibrio cholerae of El Tor biovar containing one of the key pathogenicity genes, tcpA, is studied along with the phylogenetic relationships between these strains and toxigenic isolates. Comparative analysis of the whole genome nucleotide sequences demonstrates for the first time that ctxA^–tcpA⁺ strains vary considerably and can be clustered into two separate groups, the CTX_φ–RS1_φ⁺VPI⁺VSP⁺/CTX_φ–RS1_φ–VPI⁺VSP⁺ isolates and the CTX_φ–RS1_φ–VPI⁺VSP^– isolates, differing in their epidemiological significance. In the course of model experiments, it is established that nontoxigenic potentially epidemic CTX_φ–RS1_φ⁺VPI⁺VSP⁺/CTX_φ–RS1_φ–VPI⁺VSP⁺ isolates are derivatives of toxigenic strains. The results of whole genome SNP analysis of 35 Vibrio cholerae strains confirm these data and indicate genetic remoteness of nontoxigenic CTX_φ–RS1_φ–VPI⁺VSP^– strains both from the potentially epidemic strains and from the toxigenic isolates. It is found that the genomes of the CTX_φ–RS1_φ–VPI⁺VSP^– strains contain unique SNPs which are characteristic of them alone. The new data on the structure of the genome of nontoxigenic strains with different epidemiological significance may be further used for their genetic differentiation.