The established phylogeny of the etiological agent of plague, Yersinia pestis, is not perfect, as it does not take into account the strains from numerous natural foci of Commonwealth of Independent States (CIS). We have carried out PCR and SNP typing of 359 strains and whole genome sequencing of 51 strains from these plague foci and determined the phylogenetic diversity of the strains circulating here. They belong to 0.ANT3, 0.ANT5, 2.ANT3, 4.ANT branches of antique biovar, 2.MED0, 2.MED1 branches of medieval biovar and to 0.PE2, 0.PE4a. 0.PE4h, 0.PE4t branches. Based on the studies of 178 strains from 23 plague foci of CIS countries, it was determined that the population structure of 2.MED strains is subdivided into Caucasian–Caspian and Central Asian–Chinese branches. In Central-Caucasian high-mountain plague foci in the Russian Federation (RF) the most deeply diverged branch of medieval biovar, 2.MED0, has been found. With the data obtained, the current population structure of Y. pestis species has been refined. New subspecies classification is developed, comprising seven subspecies: pestis, caucasica (0.PE2), angolica (0.PE3), central asiatica (0.PE4), tibetica (0.PE7), ulegeica (0.PE5), and qinghaica (0.PE10).

Fifty six Yersinia pestis strains, isolated over the period of more than 50 years in three high-mountain foci of Kyrgyzstan (Tien Shan, Alai, and Talas), have been characterized by means of PCR and single nucleotide polymorphism (SNP) typing methods. Seven of these strains were also characterized by means of whole genome sequencing and genome-wide SNP phylogenetic analysis. It was found that forty two strains belong to 0.ANT2, 0.ANT3 and 0.ANT5 phylogenetic branches. From these, strains of 0.ANT2 and 0.ANT3 branches were earlier detected in China only, whereas 0.ANT5 phylogenetic branch was identified for Y. pestis phylogeny for the first time. According to the results of genome-wide SNP analysis, 0.ANT5 strains are ones of the most closely related to Y. pestis strain responsible for the Justinianic Plague. We have also found out that four of the studied strains belong to the phylogenetic branch 2.MED1, and ten strains from Talas high-mountain focus belong to the phylogenetic branch 0.PE4 (sub-branch 0.PE4t). Established diversity of Y. pestis strains and extensive dissemination of the strains pertaining to the 0.ANT branch confirm the antiquity of the mentioned above plague foci and suggest that strains of the 0.ANT branch, which serve as precursors for all highly virulent Y. pestis strains, had their origin in the Tien Shan mountains.

According to the whole genome SNP analysis of 38 Yersinia pestis strains isolated in the foci of the Northern Caspian and Northern Aral Sea regions in the 20th–early 21st centuries, between 1912 and 2015, the spatial and temporal structure of the 2.MED population of a medieval biovar in this region was determined. A phylogenetic branch 2.MED4 was identified which preceded the 2.MED1 branch that diverged later. 2.MED1 strains became the etiological agent of high-mortality plague outbreaks that occurred in the Northern Caspian region at the beginning of the 20th century. Later in the 20th century, the 2.MED1 branch became widespread in the Caspian Sea region, Caucasus, and vast areas of Central Asia. Based on the data of phylogenetic analysis, as well as epidemiological and epizootiological data, we reconstructed the paths of spread of the 2.MED1 branch in the Northern Caspian Sea region and in the Northern subzone of the Central Asian deserts. It is shown, that the reason for the activation of plague foci in the Northern Caspian region in the second half of the 20th century after a long inter-epizootic period caused by cyclical climate warming was the return of 2.MED1 from the foci of the Northern Aral Sea region. This led to the formation of stable plague foci in the Northern Caspian Sea region and Pre-Caucasus, which manifested epizootic activity in the second half of the 20th and early 21st centuries.

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