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.
We announce the genome sequences of five historical highly virulent Yersinia pestis strains of the phylogroups 2.MED4 and 2.MED1 of the medieval biovar. They were the etiological agents of plague outbreaks with high mortality rates in the Northern Caspian Sea region at the end of the 19th century and beginning of the 20th.
раСПроСтранение Yersinia pestis СредневеКового Биовара в Северном, Северо-ЗаПадном ПриКаСПии и ПредКавКаЗье во второй Половине XX веКа 1 ФКУЗ «Российский научно-исследовательский противочумный институт «Микроб», Саратов, Российская Федерация; 2 РГП на ПХВ «Национальный научный центр особо опасных инфекций им. М. Айкимбаева» Министерства здравоохранения Республики Казахстан, Алматы, Республика Казахстан; 3 РГУ «Уральская противочумная станция» Комитета охраны общественного здоровья Министерства здравоохранения Республики Казахстан, Уральск, Республика Казахстан цель работы -установление происхождения штаммов Y. pestis, получивших распространение в природных очагах чумы северного, северо-западного прикаспия и предкавказья во второй половине XX века. материалы и методы. проведено исследование свойств и полногеномное секвенирование 22 штаммов Y. pestis, выделенных в 1923-2003 гг. в пяти природных очагах сусликового типа, расположенных в северном и северо-западном прикаспии и предкавказье. Филогенетический анализ выполнен по данным полногеномного SNP анализа на основе 1348 выявленных SNPs. поиск SNPs в коровом геноме проведен с помощью программы Wombac 2.0. для анализа филогенетических связей штаммов использована дендрограмма Maximum Likelihood, модель GTR. результаты и обсуждение. все исследованные штаммы из очагов северного, северо-западного прикаспия и предкавказья относятся к филогенетической ветви 2.MED1 средневекового биовара возбудителя чумы. по данным полногеномного SNP анализа выявлено наличие двух групп близкородственных штаммов, включающих штаммы 1923-1945 и 1962-2003 гг. предшественниками штаммов 1962-2003 гг. из северного, северо-западного прикаспия и предкавказья на филогенетическом дереве являются штаммы из северного приаралья 1945 г. это свидетельствует о том, что синхронная активизация группы природных очагов прикаспийской низменности и предкавказья в 1975-1979 гг., после длительных 20-37-летних перерывов, могла быть вызвана распространением штаммов из северного приаралья. данные эпизоотических наблюдений указывают на то, что активизация волго-уральского песчаного очага чумы в 60-х годах прошлого столетия предшествовала началу регистрации эпизоотий чумы на территории природных очагов сусликового типа в северном, северо-западном прикаспии и в предкавказье.Ключевые слова: возбудитель чумы, природные очаги прикаспия, штаммы, распространение.Abstract.
Objective of the study – comparative phylogenetic analysis of Yersinia pestis strains, isolated in Precaspian North-Western steppe focus in 1924–1926, 1972, and 1986–1990 to understand the causes of focal reactivation during different time periods of the XX century.Materials and methods. The work included 30 strains of Yersinia pestis from Precaspian North-Western steppe natural focus and adjacent plague foci. Whole genome sequencing of eight Y. pestis strains from the former was carried out. Also whole-genome sequences of 16 strains from neighboring natural foci were used. Whole-genome sequencing of Y. pestis strains was conducted in Ion PGM system (Life technologies). SNPs search across the core genome was performed using software package Wombac 2.0. Tree diagram Maximum Likelihood, HKU85 model, was constructed to analyze phylogenetic relations.Results and discussion. It is established that in early XX century (1924–1926), strains of phylogenetic branches 2.MED4 and 2.MED1, belonging to medieval biovar, main subspecies, circulated on Ergenin Upland in the Precaspian North-Western steppe natural focus. Later on they became extinct in the territory. It is shown that the strains, isolated on Ergenin Upland in 1972, constituted a common subcluster on the dendrogram with the strains from low-mountain and piedmont plague foci of Caucasus and Transcaucasia, dated the same time period. It was inferred that epizootic manifestations on Ergenin upland in 1972, after a long recess since 1938, were caused by importation of Y. pestis strains from low-mountain natural plague foci of Caucasus and Transcaucasia. It was noted that expansion of Caucasian strains was of short-term character, and plague infected animals have not been found on Ergenin Upland since 1974 (including modern period). It is established that Y. pestis strains isolated in the eastern part of Precaspian North-Western steppe focus between 1986 and 1990, do not have close genetic relation to the strains that circulated on Ergenin Upland in 1924–1926 and 1972. It is determined that each epizootic period (1913–1938 and 1972–1973) in Precaspian North-Western steppe natural focus culminated in the elimination of the circulating Y. pestis strains and rehabilitation of the focal territory.
Objective of the study was to analyze phylogenetic relation of the strains and dissemination routes of Yersinia pestis in Kara Kum desert focus in XX century.Materials and methods. We have carried out whole genome sequencing of 8 Yersinia pestis strains isolated in Kara Kum desert focus between 1949 and 1985. We also used nucleotide sequences of 16 Y. pestis strains from neighboring foci of East and North Caspian Sea region dated 1917–2002, sequenced at the premises of RusRAPI “Microbe” on Genestudio Ion S5XL platform (Thermo Fischer Scientific). Phylogenetic analysis was performed based on 1720 identified core SNPs. Phylogenetic dendrogram was constructed using Maximum Likelihood algorithm, PhyML v. 3.1 software package, and nucleotide substitution model GTR.Results and discussion. On the basis of whole-genome SNP analysis of Y. pestis strains from Kara Kum desert focus, West and North Caspian Sea region foci analysis of plague agent populations circulating in Turkmenistan in XX century was conducted. It has been demonstrated that three separate waves of Y. pestis dissemination swept the territory of Kara Kum desert focus. The origin of the first one, registered in 1912, plague outbreak in south-eastern part of the focus and its etiological agent remain unspecified so far. The second wave is associated with distribution of North-Aral 2.MED1 population of medieval biovar in 1949–1970, which led to the emergence of epizootic activity in 1949, as well as subsequent cases and outbreaks of plague in this territory in the middle of the XX century. In the mid-second half of the past century, one more 2. MED1 dissemination wave from the North Balkhash region hit the Kara Kum desert focus. This central-asian population has also taken root in the natural biocoenosis of the Kara Kum focus. The data obtained testify to active processes of distribution of Y. pestis of medieval biovar in East Caspian Sea region in southern sub-zone of Eurasian deserts in XX century.
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