Qinghai Institute for Endemic Disease Prevention and Control, Xining, People's Republic of China.
Key Laboratory for Plague Prevention and Control of Qinghai Province, Xining, People's Republic of China.
PLoS Negl Trop Dis. 2018 Jun 25;12(6):e0006579. doi: 10.1371/journal.pntd.0006579. eCollection 2018 Jun.
Plague, caused by the bacterium Yersinia pestis, is a highly infectious, zoonotic disease. Hundreds of human plague cases are reported across the world annually. Qinghai Plateau is one of the most severely affected plague regions in China, with more than 240 fatal cases of Y. pestis in the last 60 years. Conventional epidemiologic analysis has effectively guided the prevention and control of local plague transmission; however, molecular genetic analysis is more effective for investigating population diversity and transmission. In this report, we employed different genetic markers to analyze the population structure of Y. pestis in Qinghai Plateau.
METHODOLOGY/PRINCIPAL FINDING: We employed a two-step hierarchical strategy to analyze the phylogeny of 102 Qinghai Plateau isolates of Y. pestis, collected between 1954 and 2011. First, we defined the genealogy of Y. pestis by constructed minimum spanning tree based on 25 key SNPs. Seven groups were identified, with group 1.IN2 being identified as the dominant population. Second, two methods, MLVA and CRISPR, were applied to examine the phylogenetic detail of group 1.IN2, which was further divided into three subgroups. Subgroups of 1.IN2 revealed a clear geographic cluster, possibly associated with interaction between bacteriophage and Y. pestis. More recently, Y. pestis populations appear to have shifted from the east toward the center and west of Qinghai Plateau. This shift could be related to destruction of the local niche of the original plague focus through human activities. Additionally, we found that the abundance and relative proportion of 1.IN2 subgroups varied by decade and might be responsible for the fluctuations of plague epidemics in Qinghai Plateau.
CONCLUSION/SIGNIFICANCE: Molecular genotyping methods provided us with detailed information on population diversity and the spatial-temporal distribution of dominant populations of Y. pestis, which will facilitate future surveillance, prevention, and control of plague in Qinghai Plateau.
鼠疫是由鼠疫耶尔森菌引起的一种高度传染性的人畜共患病,全球每年报告数百例人间鼠疫病例。青藏高原是中国受鼠疫影响最严重的地区之一,在过去的 60 年中,已有超过 240 例鼠疫耶尔森菌致死病例。传统的流行病学分析有效地指导了当地鼠疫传播的预防和控制;然而,分子遗传学分析对于研究种群多样性和传播更为有效。在本报告中,我们采用不同的遗传标记分析了青藏高原鼠疫耶尔森菌的种群结构。
方法/主要发现:我们采用两步分层策略分析了 1954 年至 2011 年间采集的 102 株青藏高原鼠疫耶尔森菌的系统发育。首先,我们构建了基于 25 个关键 SNP 的最小生成树,定义了鼠疫耶尔森菌的系统发育。共鉴定出 7 个群,其中群 1.IN2 为优势种群。其次,我们应用 MLVA 和 CRISPR 两种方法对群 1.IN2 的系统发育细节进行了检验,进一步将其分为三个亚群。1.IN2 亚群呈现出明显的地理聚类,可能与噬菌体和鼠疫耶尔森菌的相互作用有关。最近,鼠疫耶尔森菌种群似乎已经从东部向青藏高原的中心和西部转移。这种转移可能与人类活动破坏了原有鼠疫疫源地的局部小生境有关。此外,我们发现 1.IN2 亚群的丰度和相对比例随十年变化而变化,可能是青藏高原鼠疫流行波动的原因。
结论/意义:分子基因分型方法为我们提供了鼠疫耶尔森菌种群多样性和优势种群时空分布的详细信息,这将有助于未来对青藏高原鼠疫的监测、预防和控制。