The genetic diversity of Yersinia pestis, the etiologic agent of plague, is extremely limited because of its recent origin coupled with a slow clock rate. Here we identified 2,326 SNPs from 133 genomes of Y. pestis strains that were isolated in China and elsewhere. These SNPs define the genealogy of Y. pestis since its most recent common ancestor. All but 28 of these SNPs represented mutations that happened only once within the genealogy, and they were distributed essentially at random among individual genes. Only seven genes contained a significant excess of nonsynonymous SNP, suggesting that the fixation of SNPs mainly arises via neutral processes, such as genetic drift, rather than Darwinian selection. However, the rate of fixation varies dramatically over the genealogy: the number of SNPs accumulated by different lineages was highly variable and the genealogy contains multiple polytomies, one of which resulted in four branches near the time of the Black Death. We suggest that demographic changes can affect the speed of evolution in epidemic pathogens even in the absence of natural selection, and hypothesize that neutral SNPs are fixed rapidly during intermittent epidemics and outbreaks.infectious disease | molecular clock | phylogenomics | NGS | molecular epidemiology

Background Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood.Methods and FindingsTo elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of ∼89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence.ConclusionsTo our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.

Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity.

Background Vibrio parahaemolyticus is a leading cause of infectious diarrhea and enterogastritis via the fecal-oral route. V. harveyi is a pathogen of fishes and invertebrates, and has been used as a model for quorum sensing (QS) studies. LuxR is the master QS regulator (MQSR) of V. harveyi , and LuxR-dependent expression of its own gene, qrr2–4 and aphA have been established in V. harveyi . Molecular regulation of target genes by the V. parahaemolyticus MQSR OpaR is still poorly understood. Methodology/Principal Findings The bioinformatics analysis indicated that V. parahaemolyticus OpaR, V. harveyi LuxR, V. vulnificu SmcR, and V. alginolyticus ValR were extremely conserved, and that these four MQSRs appeared to recognize the same conserved cis -acting signals, which was represented by the consensus constructs manifesting as a position frequency matrix and as a 20 bp box, within their target promoters. The MQSR box-like sequences were found within the upstream DNA regions of opaR , qrr2–4 and aphA in V. parahaemolyticus , and the direct transcriptional regulation of these target genes by OpaR were further confirmed by multiple biochemical experiments including primer extension assay, gel mobility shift assay, and DNase I footprinting analysis. Translation and transcription starts, core promoter elements for sigma factor recognition, Shine-Dalgarno sequences for ribosome recognition, and OpaR-binding sites were determined for the five target genes of OpaR, which gave a structural map of the OpaR-dependent promoters. Further computational promoter analysis indicated the above regulatory circuits were shared by several other closely related Vibrios but with slight exceptions. Conclusions/Significance This study gave a comprehensive computational and characterization of the direct transcriptional regulation of five target genes, opaR , qrr2–4 and ahpA , by OpaR in V. parahaemolyticus . These characterized regulatory circuits were conserved in V. harveyi and V. parahaemolyticus .