Streptococcus suis is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for S. suis infection. We created Tn-Seq libraries in a virulent S. suis strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in ex vivo models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in S. suis pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.

中文翻译：

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猪猪链球菌感染的条件必需基因的鉴定。

猪链球菌是革兰氏阳性细菌和人畜共患病原体，可引起猪和人的脑膜炎和败血症。这项研究的目的是确定猪链球菌感染所需的基因。我们在有毒的猪链球菌10号菌株中创建了Tn-Seq库，该菌株用于在鞘内实验感染中接种猪。从感染的不同部位（血液，脑脊髓液和脑膜）恢复的突变体的相对丰度的比较分析确定了361个有条件的必需基因，即感染所需的基因，约占基因组的18％。有条件的必需基因主要参与代谢和转运过程，调节，核糖体结构和生物发生，转录以及细胞壁膜和包膜的生物发生，压力防御和免疫逃避。在一组具有不同遗传本体的10个基因中创建了定向突变体，并在离体模型中确定了它们的作用。与野生型相比，突变株在全血，血清，脑脊髓液，热休克和应激条件下对存活的敏感性不同。另外，在共感染实验中验证了三个选择的突变体的作用，在共感染实验中，猪被野生型和等基因突变株感染。在这项工作中确定的感染的遗传决定因素有助于猪链球菌发病机理的新见解，并可作为新型疫苗或抗菌药物的靶标。与野生型相比，脑脊液，热休克和压力状况。另外，在共感染实验中验证了三个选择的突变体的作用，在共感染实验中，猪被野生型和等基因突变株感染。这项工作中确定的感染的遗传决定因素有助于猪链球菌发病机理的新见解，并可作为新型疫苗或抗菌药物的靶标。与野生型相比，脑脊液，热休克和压力状况。另外，在共感染实验中验证了三个选择的突变体的作用，在共感染实验中，猪被野生型和等基因突变株感染。这项工作中确定的感染的遗传决定因素有助于猪链球菌发病机理的新见解，并可作为新型疫苗或抗菌药物的靶标。