Epidemic and pandemic clones of bacterial pathogens with distinct characteristics continually emerge, replacing those previously dominant through mechanisms that remain poorly characterized. Here, whole-genome-sequencing-powered epidemiology linked horizontal transfer of a virulence gene, sopE, to the emergence and clonal expansion of a new epidemic Salmonella enterica serovar Typhimurium (S. Typhimurium) clone. The sopE gene is sporadically distributed within the genus Salmonella and rare in S . enterica Typhimurium lineages, but was acquired multiple times during clonal expansion of the currently dominant pandemic monophasic S. Typhimurium sequence type (ST) 34 clone. Ancestral state reconstruction and time-scaled phylogenetic analysis indicated that sopE was not present in the common ancestor of the epidemic clade, but later acquisition resulted in increased clonal expansion of sopE-containing clones that was temporally associated with emergence of the epidemic, consistent with increased fitness. The sopE gene was mainly associated with a temperate bacteriophage mTmV, but recombination with other bacteriophage and apparent horizontal gene transfer of the sopE gene cassette resulted in distribution among at least four mobile genetic elements within the monophasic S . enterica Typhimurium ST34 epidemic clade. The mTmV prophage lysogenic transfer to other S. enterica serovars in vitro was limited, but included the common pig-associated S . enterica Derby (S. Derby). This may explain mTmV in S. Derby co-circulating on farms with monophasic S. Typhimurium ST34, highlighting the potential for further transfer of the sopE virulence gene in nature. We conclude that whole-genome epidemiology pinpoints potential drivers of evolutionary and epidemiological dynamics during pathogen emergence, and identifies targets for subsequent research in epidemiology and bacterial pathogenesis.

中文翻译：

---

全基因组流行病学将噬菌体介导的毒力基因获取与大流行性肠沙门氏菌血清型鼠伤寒克隆的克隆扩增联系起来


具有独特特征的流行病和大流行性细菌病原体克隆不断出现，通过仍不明确的机制取代以前占主导地位的克隆。在这里，全基因组测序驱动的流行病学将毒力基因sopE的水平转移与新的流行性肠沙门氏菌鼠伤寒血清型 ( S. Typhimurium) 克隆的出现和克隆扩展联系起来。 sopE基因零星分布在沙门氏菌属内，在沙门氏菌属中很少见。肠杆菌伤寒沙门氏菌谱系，但在目前占主导地位的大流行单相沙门氏菌克隆扩增过程中多次获得。鼠伤寒序列类型 (ST) 34 克隆。祖先状态重建和时间尺度的系统发育分析表明， sopE并不存在于流行病分支的共同祖先中，但后来的获得导致含有sopE的克隆的克隆扩张增加，这在时间上与流行病的出现相关，这与流行病的出现一致。健康。 sopE基因主要与温带噬菌体mTmV相关，但与其他噬菌体的重组和sopE基因盒的明显水平基因转移导致在单相S中至少四个可移动遗传元件之间的分布。鼠伤寒肠杆菌 ST34 流行分支。 mTmV 原噬菌体在体外向其他肠沙门氏菌血清型的溶原性转移是有限的，但包括常见的猪相关沙门氏菌。肠德比 ( S. Derby)。这可以解释S中的 mTmV 。 Derby 在农场与单相S共同循环。 Typhimurium ST34，强调了sopE毒力基因在自然界中进一步转移的潜力。我们得出的结论是，全基因组流行病学查明了病原体出现期间进化和流行病学动态的潜在驱动因素，并确定了流行病学和细菌发病机制的后续研究目标。