mStrain: strain-level identification of Yersinia pestis using metagenomic data.

Motivation: High-resolution target pathogen detection using metagenomic sequencing data represents a major challenge due to the low concentration of target pathogens in samples. We introduced mStrain, a novel Yesinia pestis strain/lineage-level identification tool that utilizes metagenomic data. mStrain successfully identified Y. pestis at the strain/lineage level by extracting sufficient information regarding single-nucleotide polymorphisms (SNPs), which can therefore be an effective tool for identification and source tracking of Y. pestis based on metagenomic data during a plague outbreak. Definition: . Strain-level identification: Assigning the reads in the metagenomic sequencing data to an exactly known or most closely representative Y. pestis strain. Lineage-level identification: Assigning the reads in the metagenomic sequencing data to a specific lineage on the phylogenetic tree. canoSNPs: The unique and typical SNPs present in all representative strains. Ancestor/derived state: An SNP is defined as the ancestor state when consistent with the allele of Yersinia pseudotuberculosis strain IP32953; otherwise, the SNP is defined as the derived state. Availability and implementation: The code for running mStrain, the test dataset, and instructions for running the code can be found at the following GitHub repository: https://github.com/xwqian1123/mStrain.

Genomic diversity of Yersinia pestis from Yunnan Province, China, implies a potential common ancestor as the source of two plague epidemics.

Plague, caused by Yersinia pestis, is a zoonotic disease that can reemerge and cause outbreaks following decades of latency in natural plague foci. However, the genetic diversity and spread pattern of Y. pestis during these epidemic-silent cycles remain unclear. In this study, we analyze 356 Y. pestis genomes isolated between 1952 and 2016 in the Yunnan Rattus tanezumi plague focus, China, covering two epidemic-silent cycles. Through high-resolution genomic epidemiological analysis, we find that 96% of Y. pestis genomes belong to phylogroup 1.ORI2 and are subdivided into two sister clades (Sublineage1 and Sublineage2) characterized by different temporal-spatial distributions and genetic diversity. Most of the Sublineage1 strains are isolated from the first epidemic-silent cycle, while Sublineage2 strains are predominantly from the second cycle and revealing a west to east spread. The two sister clades evolved in parallel from a common ancestor and independently lead to two separate epidemics, confirming that the pathogen responsible for the second epidemic following the silent interval is not a descendant of the causative strain of the first epidemic. Our results provide a mechanism for defining epidemic-silent cycles in natural plague foci, which is valuable in the prevention and control of future plague outbreaks.

Genomic epidemiological analysis of county-scale Yersinia pestis spread pattern over 50 years in a Southwest Chinese prefecture.

Plague, one of the most devastating infectious diseases in human history, is caused by the bacterium Yersinia pestis. Since the 1950s, the Dehong Dai-Jingpo Autonomous Prefecture (DH) in Yunnan Province, China, has recorded plague outbreaks that have resulted in 1,153 human cases and 379 deaths. The genetic diversity and transmission characteristics of Y. pestis strains in this region remain unknown. Here, we performed high-resolution genomic epidemiological analysis of 175 Y. pestis strains isolated from five counties and 19 towns in DH between 1953 and 2007. Phylogenetic analysis revealed that most DH strains were located in lineage 1.ORI2, which could be further subdivided into seven sub-phylogroups (SPG1-SPG7). The dominant sub-phylogroups of Y. pestis in DH varied during different periods and presented a population shift. Genomic evidence showed that plague might have emerged from the southwest of DH (e.g., Longchuan or Ruili counties) or its bordering countries, and subsequently spread to the northeast in multiple waves between 1982 and 2007. Our study infers a fine-scale phylogeny and spread pattern of the DH Y. pestis population, which extends our knowledge regarding its genetic diversity and provides clues for the future prevention and control of plague in this region.