The Wellcome Trust Sanger Institute, the Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
mBio. 2013 Aug 27;4(5):e00565-13. doi: 10.1128/mBio.00565-13.
Salmonella enterica serovar Typhimurium definitive type 2 (DT2) is host restricted to Columba livia (rock or feral pigeon) but is also closely related to S. Typhimurium isolates that circulate in livestock and cause a zoonosis characterized by gastroenteritis in humans. DT2 isolates formed a distinct phylogenetic cluster within S. Typhimurium based on whole-genome-sequence polymorphisms. Comparative genome analysis of DT2 94-213 and S. Typhimurium SL1344, DT104, and D23580 identified few differences in gene content with the exception of variations within prophages. However, DT2 94-213 harbored 22 pseudogenes that were intact in other closely related S. Typhimurium strains. We report a novel in silico approach to identify single amino acid substitutions in proteins that have a high probability of a functional impact. One polymorphism identified using this method, a single-residue deletion in the Tar protein, abrogated chemotaxis to aspartate in vitro. DT2 94-213 also exhibited an altered transcriptional profile in response to culture at 42°C compared to that of SL1344. Such differentially regulated genes included a number involved in flagellum biosynthesis and motility. IMPORTANCE Whereas Salmonella enterica serovar Typhimurium can infect a wide range of animal species, some variants within this serovar exhibit a more limited host range and altered disease potential. Phylogenetic analysis based on whole-genome sequences can identify lineages associated with specific virulence traits, including host adaptation. This study represents one of the first to link pathogen-specific genetic signatures, including coding capacity, genome degradation, and transcriptional responses to host adaptation within a Salmonella serovar. We performed comparative genome analysis of reference and pigeon-adapted definitive type 2 (DT2) S. Typhimurium isolates alongside phenotypic and transcriptome analyses, to identify genetic signatures linked to host adaptation within the DT2 lineage.
肠炎沙门氏菌 Typhimurium 定型 2 型（DT2）仅限于 Columba livia（岩鸽或野鸽）宿主，但也与在牲畜中循环并引起以人类肠胃炎为特征的人畜共患病的沙门氏菌 Typhimurium 分离株密切相关。根据全基因组序列多态性，DT2 分离株在肠炎沙门氏菌 Typhimurium 内形成一个独特的系统发育群。对 DT2 94-213 与肠炎沙门氏菌 Typhimurium SL1344、DT104 和 D23580 的比较基因组分析发现，除了噬菌体内的变异外，基因内容几乎没有差异。然而，DT2 94-213 携带 22 个假基因，而其他密切相关的肠炎沙门氏菌 Typhimurium 株则完整保留这些假基因。我们报告了一种新的基于计算机的方法来鉴定具有高功能影响概率的蛋白质中的单个氨基酸取代。使用这种方法鉴定的一个多态性是 Tar 蛋白中的单个残基缺失，该缺失破坏了体外对天冬氨酸的趋化性。与 SL1344 相比，DT2 94-213 在 42°C 培养时的转录谱也发生了改变。这种差异调节的基因包括许多参与鞭毛生物合成和运动的基因。重要的是，尽管肠炎沙门氏菌 Typhimurium 可以感染广泛的动物物种，但该血清型的一些变体表现出更有限的宿主范围和改变的疾病潜力。基于全基因组序列的系统发育分析可以识别与特定毒力特征相关的谱系，包括宿主适应性。本研究是首次将与病原体特异性相关的遗传特征（包括编码能力、基因组降解和对宿主适应的转录反应）联系起来的研究之一肠炎沙门氏菌血清型内。我们对参考和适应鸽子的定型 2 型（DT2）肠炎沙门氏菌 Typhimurium 分离株进行了比较基因组分析，以及表型和转录组分析，以确定与 DT2 谱系内宿主适应性相关的遗传特征。
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