Genome Sequence of the Deep-Rooted Yersinia pestis Strain Angola Reveals New Insights into the Evolution and Pangenome of the Plague Bacterium

Abstract

To gain insights into the origin and genome evolution of the plague bacterium Yersinia pestis, we have sequenced the deep-rooted strain Angola, a virulent Pestoides isolate. Its ancient nature makes this atypical isolate of particular importance in understanding the evolution of plague pathogenicity. Its chromosome features a unique genetic make-up intermediate between modern Y. pestis isolates and its evolutionary ancestor, Y. pseudotuberculosis. Our genotypic and phenotypic analyses led us to conclude that Angola belongs to one of the most ancient Y. pestis lineages thus far sequenced. The mobilome carries the first reported chimeric plasmid combining the two species-specific virulence plasmids. Genomic findings were validated in virulence assays demonstrating that its pathogenic potential is distinct from modern Y. pestis isolates. Human infection with this particular isolate would not be diagnosed by the standard clinical tests, as Angola lacks the plasmid-borne capsule, and a possible emergence of this genotype raises major public health concerns. To assess the genomic plasticity in Y. pestis, we investigated the global gene reservoir and estimated the pangenome at 4,844 unique protein-coding genes. As shown by the genomic analysis of this evolutionary key isolate, we found that the genomic plasticity within Y. pestis clearly was not as limited as previously thought, which is strengthened by the detection of the largest number of isolate-specific single-nucleotide polymorphisms (SNPs) currently reported in the species. This study identified numerous novel genetic signatures, some of which seem to be intimately associated with plague virulence. These markers are valuable in the development of a robust typing system critical for forensic, diagnostic, and epidemiological studies.

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

“…Mutations accumulate rapidly among "mutator" strains with elevated spontaneous mutation rates (32). However, Angola in 0.PE3, the strain whose genome had the most SNPs, is not a mutator (33), nor did any of the genomes contain traces of the epistatic mutations that can result in reversion of a transient mutator to wild-type. Furthermore, only one mutator was identified among 294 Y. pestis strains from global sources (13).…”

Evolutionary Dynamics of the Yersinia enterocolitica Complex

“…As it presents an outwardly displayed antigen, it might be important in the interaction between the bacterium and host cells, especially of the immune response, and has been the target for vaccine development against plague (Carniel, 2002;Eppinger, et al, 2010). Capsule-deficient Y. pestis biovar Angola was shown to lack lethality in the guinea pig model after subcutaneous infection, and was also less virulent in the subcutaneous mouse model but not in the aerosol model .…”

“…The transposase can mediate the transposition of the element to a different genomic location. Recombination between IS elements have led to wide-ranged genome rearrangements in Y. pestis, which are still ongoing in culture in vivo (Parkhill, et al, 2001a;Deng, et al, 2002;Chain, et al, 2004;Eppinger, et al, 2010). IS elements have inserted into the coding sequences of other genes, thus disrupting the expression of functional proteins and promoting isolatespecific polymorphisms (Parkhill, et al, 2001a;Chain, et al, 2004;Eppinger, et al, 2010).…”

“…Compared to Y. pseudotuberculosis, the Y. pestis genome shows an increase in the number of insertion sequence (IS) elements that are present (Parkhill, et al, 2001a;Deng, et al, 2002;Wren, 2003;Chain, et al, 2004;Eppinger, et al, 2007;Eppinger, et al, 2010). IS elements are DNA sections encoding a transposase flanked by perfect inverted repeats.…”

“…Eppinger, et al (2010) describe a chimeric plasmid pMT-PCP consisting of a cointegrate of a single copy of pMT1 and two copies of pPCP1 in Y. pestis biovar Pestoides strain Angola. Some other Pestoides isolates were shown to lack one of the two plasmids, indicating that virulence plasmids play an important role in disease but are not predominant .…”