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首页> 外文期刊>Applied Microbiology >Identification of Natural Mutations Responsible for Altered Infection Phenotypes of Salmonella enterica Clinical Isolates by Using Cell Line Infection Screens
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Identification of Natural Mutations Responsible for Altered Infection Phenotypes of Salmonella enterica Clinical Isolates by Using Cell Line Infection Screens

机译：用细胞系感染筛网鉴定负责沙门氏菌肠道临床分离株的改变感染表型的自然突变

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The initial steps of Salmonella pathogenesis involve adhesion to and invasion into host epithelial cells. While well-studied for Salmonella enterica serovar Typhimurium, the factors contributing to this process in other, host-adapted serovars remains unexplored. Here, we screened clinical isolates of serovars Gallinarum, Dublin, Choleraesuis, Typhimurium, and Enteritidis for adhesion to and invasion into intestinal epithelial cell lines of human, porcine, and chicken origins. Thirty isolates with altered infectivity were used for genomic analyses, and 14 genes and novel mutations associated with high or low infectivity were identified. The functions of candidate genes included virulence gene expression regulation and cell wall or membrane synthesis and components. The role of several of these genes in Salmonella adhesion to and invasion into cells has not previously been investigated. The genes dksA (encoding a stringent response regulator) and sanA (encoding a vancomycin high-temperature exclusion protein) were selected for further analyses, and we confirmed their roles in adhesion to and invasion into host cells. Furthermore, transcriptomic analyses were performed for S . Enteritidis and S . Typhimurium, with two highly infective and two marginally infective isolates for each serovar. Expression profiles for the isolates with altered infection phenotypes revealed the importance of type 3 secretion system expression levels in the determination of an isolate’s infection phenotype. Taken together, these data indicate a new role in cell host infection for genes or gene variants previously not associated with adhesion to and invasion into the epithelial cells.IMPORTANCE Salmonella is a foodborne pathogen affecting over 200 million people and resulting in over 200,000 fatal cases per year. Its adhesion to and invasion into intestinal epithelial cells represent one of the first and key steps in the pathogenesis of salmonellosis. Still, around 35 to 40% of bacterial genes have no experimentally validated function, and their contribution to bacterial virulence, including adhesion and invasion, remains largely unknown. Therefore, the significance of this study is in the identification of new genes or gene allelic variants previously not associated with adhesion and invasion. It is well established that blocking adhesion and/or invasion would stop or hamper bacterial infection; therefore, the new findings from this study could be used in future developments of anti- Salmonella therapy targeting genes involved in these key processes. Such treatment could be a valuable alternative, as the prevalence of antibiotic-resistant bacteria is increasing very rapidly.
机译：沙门氏菌发病机制的初始步骤涉及与宿主上皮细胞的粘附和侵袭。虽然研究了Salmonella Serovar Typhimurium，但在其他宿主适应的Serovars中有助于这种过程的因素仍未开发。在此，我们筛查塞洛达拉利人，都伯林，霍乱症，血小场和肠炎患者的临床分离株，以粘附和侵袭人，猪和鸡起源的肠上皮细胞系。具有改变的感染性的30分离株用于基因组分析，并确定具有高或低感染性相关的14个基因和新的突变。候选基因的功能包括毒力基因表达调控和细胞壁或膜合成和组分。此外，还没有先研究多种这些基因在沙门氏菌中的粘附和侵入细胞中的作用。选择DKSA（编码严格响应调节剂）和SANA（编码万古霉素高温排除蛋白）以进一步分析，并且我们证实了它们的粘附性和侵入到宿主细胞中的作用。此外，进行转录组分析。 Enteritidis和s。施鼠，两个高度感染性和每个塞洛伐克的两个边缘感染性分离物。具有改变的感染表型的分离物的表达谱揭示了3型分泌系统表达水平在测定分离的感染表型中的重要性。这些数据表明，对于先前没有与上皮细胞的粘附和侵袭相关的基因或基因变体的基因或基因变体中的新作用。分析沙门氏菌是影响超过2亿人的食源性病原体，导致每年有超过20万人的致命病例年。它的粘附性和侵袭到肠上皮细胞代表了沙门氏菌病发病机制中的第一步和关键步骤之一。仍然，大约35％至40％的细菌基因没有实验验证的功能，以及它们对细菌毒力的贡献，包括粘附和侵袭，仍然很大程度上是未知的。因此，本研究的重要性是鉴定以前与粘附和侵袭相关的新基因或基因等位基因变体。很好地确定，阻断粘附和/或侵袭将停止或妨碍细菌感染;因此，本研究的新发现可用于未来的抗沙门氏菌治疗靶向基因的未来发展这些关键过程。这种治疗可能是一个有价值的替代品，因为抗生素抗性细菌的患病率越来越快地增加。

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