Whole genome multilocus sequence typing as an epidemiologic tool for Yersinia pestis

• A whole genome sequencing "based method" for molecular epidemiological investigations of plague is evaluated.
• Whole genome multilocus sequence typing (wgMLST) combines single nucleotide polymorphisms, variable number of tandem repeats, and small insertions and deletions into a single analysis.
• wgMLST is scalable to include new alleles for every strain sequenced.
• Diversity among multi-locus sequence typing alleles accurately grouped US Yersinia pestis strains by their epidemiological relationships

Human plague is a severe and often fatal zoonotic disease caused by Yersinia pestis. For public health investigations of human cases, nonintensive whole genome molecular typing tools, capable of defining epidemiologic relationships, are advantageous. Whole genome multilocus sequence typing (wgMLST) is a recently developed methodology that simplifies genomic analyses by transforming millions of base pairs of sequence into character data for each gene. We sequenced 13 US Y. pestis isolates with known epidemiologic relationships. Sequences were assembled de novo, and multilocus sequence typing alleles were assigned by comparison against 3979 open reading frames from the reference strain CO92. Allele-based cluster analysis accurately grouped the 13 isolates, as well as 9 publicly available Y. pestis isolates, by their epidemiologic relationships. Our findings indicate wgMLST is a simplified, sensitive, and scalable tool for epidemiologic analysis of Y. pestis strains.