Single Nucleotide Polymorphisms in hsp65 and MACPPE12 Genes of Mycobacterium avium subsp. hominissuis

Mycobacterium avium subsp. hominissuis (MAH) are typical inhabitants of the environment, which are known as opportunistic pathogens of animals and humans. The aim of our study was to analyze single-nucleotide polymorphisms (SNPs) in the hsp65 and MACPPE12 genes to characterize the Russian population of MAH in the context of studying phylogenetic relationships and the evolution of geographically distant populations of M. avium subsp. hominissuis. The sequence analysis of the hsp65 and MACPPE12 genes was applied for 40 MAH strains isolated from humans (patients with mycobacteriosis). The nucleotide sequences were aligned to the reference genome of M. avium subsp. hominissuis 104 (accession no. NC_008595.1). The mutational profiles of Russian strains were compared with those isolated in other countries. In total, 40 MAH strains were classified into three different hsp65 sequevars: code 1, code 2, and code 3. The majority of MAH strains (72.5%) belonged to code 1, the same sequevar as for MAH strain 104. The sequence analysis of the MACPPE12 gene revealed 20 SNPs grouped into nine sequevars at the nucleic acid level: NA01, NA02, NA03, NA06, NA10, NA13, NA14, NA19, and NA_Rus01. Eight out of 20 SNPs were nonsynonymous, resulting in seven sequevars at the amino acid level: AA01, AA02, AA04, AA07, AA08, AA13, and AA_Rus01. The sequevar AA02 consisted of three different NA variants with synonymous SNPs profiles: NA02, NA03, and NA06. Half of the MAH strains belonged to the sequevar AA02 (type NA02). The predominant cluster AA02 (type NA02)/code 1 and the unique variant AA_Rus01 (NA_Rus01) were identified among MAH strains from Russia. Thus, we confirmed the relative conservativeness of the nucleotide sequence of the hsp65 gene but the polymorphism of the MACPPE12 gene. At the same time, a comparative analysis of the SNPs profiles of the hsp65 and MACPPE12 genes allowed us to identify differences and similarities between geographically distant populations of MAH, which highlighted the variability of the global population of M. avium species.