Variability of Multiple Resistance to Antibiotics in a Cholera Agent Associated with Different Types of SXT Element and Spontaneous Chromosome Mutations

Abstract—The aim of the study is to analyze the variability of multiple antibiotic resistance caused by variations in the mobile SXT element and chromosomal gene mutations in various strains of the cholera agent isolated in Russia and endemic cholera foci. Based on bioinformatic analysis of the whole genome nucleotide sequences of 110 clinical strains of V. cholerae El Tor isolated in different regions, the structure of their integrative conjugative SXT elements was determined. Mutations in the chromosomal antibiotic-resistance genes gyrA, parC, and carR were identified. Phylogenetic analysis of strains containing different types of SXT was carried out. It was shown that the variability of multiple antibiotic resistance in the studied strains from Russia and Ukraine was associated with the presence in the chromosome of two types of SXT elements with different compositions of resistance genes and spontaneous chromosomal mutations in the gyrA, parC, and carR genes, which determine resistance to nalidixic acid and polymyxin B. At the same time, five types of SXT were found in the studied strains from Asian and African countries, which determined a higher level of variability of their antibiotic resistance. Based on SNP analysis, an assessment of the phylogenetic relationships of isolates with different types of SXT and different chromosomal mutations is given. The data obtained indicate that the variability of cholera-agent resistance to antibiotics is provided by different types of SXT and mutations in chromosomal genes. The revealed high level of SXT genomic diversity in the V. cholerae population in cholera-endemic regions indicates the threat of importation of new cholera-agent strains with previously unknown antibiotic resistance into Russia.