Three Genetically Different Lineages of Yersinia pestis subsp. Microtus bv. Caucasica (0.PE2) Strains Circulate among Common Voles in Natural Plague Foci in the Caucasus

Gram-negative bacteria Y. pestis subsp. pestis of 0.ANT-4.ANT, 1.ORI, and 2.MED SNP types are the cause of numerous epidemic outbreaks, epidemics, and three plague pandemics, claiming hundreds of millions of human lives. At the same time, strains of the microtus subspecies that belong to the 0.PE SNP type circulating in populations of different species of voles ( Microtus spp.) are able to cause only extremely rare human infections that are not transmitted from person to person. It is suggested that the clinical form of the infection can develop only in individuals with impaired immune status. Strains of Y. pestis bv. caucasica (0.PE2), one of the most ancient phylogenetic groups of subsp. microtus , are isolated on the territory of the following natural foci: the Transcaucasian highland (including the Leninakan (4), Pre-Sevan (5), and Zanzegur- Karabakh (6)) mesofoci and the Dagestan-highland (39). In addition to the enumerated areas, similar strains of Y. pestis are isolated in the territories of the Pre-Araks focus (7) bordering the Transcaucasian highland one. Previously, we showed that passport data on the phenotypic differences of strains of the biovar caucasica, isolated from different foci, corresponded to their MLVA25, CRISPR, and DFR genotypes. In the present work, a comparative analysis of the clustering ability of MLVA25- and CRISPR-typing methods with the “gold standard” of phylogenetic studies—SNP typing—has been conducted on 21 strains of Y. pestis subsp. microtus bv. caucasica (0.PE2). The analysis of the obtained results confirms the existence of three clonal clusters of strains corresponding to the natural plague foci—39, 4, and the group of foci 5–7. Only the SNP-typing method made it possible to separate branch of focus 5 isolates from a group of strains isolated in foci 5–7. In addition, this method made it possible to reveal a greater genetic heterogeneity of strains from focus 39, in contrast to the strains of foci 4–7. When analyzing the genomes of Y. pestis strains isolated in the territory of focus 39, a deletion (~20 kb) was detected in the CRISPR region of the Ypb locus. The absence of this locus can serve as a marker for the determination of a given population of Y. pestis strains.