Genotyping and Phylogenetic Analysis of Yersinia pestis by MLVA: Insights into the Worldwide Expansion of Central Asia Plague Foci

Abstract

BackgroundThe species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical) non-human pathogenic biovar Microtus (alias Pestoides) including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar.Methodology/Principal FindingsMulti-locus VNTR analysis (MLVA) with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU), Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci.Conclusions/SignificanceThe results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA25 assay provide an unprecedented view on the expansion and microevolution of Y. pestis.

Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis

“…We sequenced 118 genomes of isolates from China, Mongolia, the former Soviet Union, Myanmar, and Madagascar using Illumina short-read sequencing (Dataset S1). The 107 Chinese isolates represent the diversity revealed by molecular genotyping of > 900 strains (14,15), which in turn reflect the geographic and temporal diversity of > 5,000 isolates collected during annual surveillance of all sylvatic plague foci in China. Thus, these genomes should provide a good representation of the geographic and genetic diversity of Y. pestis in China.…”

Identification of Variable-Number Tandem-Repeat (VNTR) Sequences in Acinetobacter baumannii and Interlaboratory Validation of an Optimized Multiple-Locus VNTR Analysis Typing Scheme

“…MLVA has become the reference typing method for Bacillus anthracis, Yersinia pestis, Mycobacterium tuberculosis, Escherichia coli O157, and Salmonella enterica (11,14,15,16,21,36) and is considered a promising alternative to established typing methods for other microbial species, including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Legionella pneumophila (13,19,20,38), especially when highly discriminatory, portable, and fast results are needed (32). Therefore, in this work, we set the basis for the application of MLVA to the epidemiological typing of A. baumannii for possible use as a complement or alternative to previously established methods.…”

Genetic diversity of Yersinia pestis in Brazil

“…However, new molecular approaches have uncovered a relatively high level of genetic diversity. The global expansion of Y. pestis strains from central Asian plague foci was demonstrated by Li et al (2009) with an MLVA of 25 VNTRs. MLVA was also successfully employed to study the maintenance and spread of Y. pestis in Madagascar (Vogler et al, 2011).…”

“…FR S and RU S were identified by in silico analysis of the Y. pestis CO92 genome sequence with the Tandem Repeats Finder software (Benson, 1999). The Li et al (2009) standardized nomenclature was used for all loci, except for ms30 (Le Flèche et al, 2001) and 1AB (Adair et al, 2000).…”