Staphylococcus lugdunensis is a coagulase negative Staphylococcus recognized as a virulent pathogen. It is responsible for a wide variety of infections, some of which are associated with biofilm production, such as implanted medical device infections or endocarditis. However, little is known about S. lugdunensis regulation of virulence factor expression. Two-component regulatory systems (TCS) play a critical role in bacterial adaptation, survival, and virulence. Among them, LytSR is widely conserved but has variable roles in different organisms, all connected to metabolism or cell death and lysis occurring during biofilm development. Therefore, we investigated here the functions of LytSR in S. lugdunensis pathogenesis. Deletion of lytSR in S. lugdunensis DSM 4804 strain did not alter either susceptibility to Triton X-100 induced autolysis or death induced by antibiotics targeting cell wall synthesis. Interestingly, ΔlytSR biofilm was characterized by a lower biomass, a lack of tower structures, and a higher rate of dead cells compared to the wild-type strain. Virulence toward Caenorhabditis elegans using a slow-killing assay was significantly reduced for the mutant compared to the wild-type strain. By contrast, the deletion of lytSR had no effect on the cytotoxicity of S. lugdunensis toward the human keratinocyte cell line HaCaT. Transcriptional analyses conducted at mid- and late-exponential phases showed that lytSR deletion affected the expression of 286 genes. Most of them were involved in basic functions such as the metabolism of amino acids, carbohydrates, and nucleotides. Furthermore, LytSR appeared to be involved in the regulation of genes encoding known or putative virulence and colonization factors, including the fibrinogen-binding protein Fbl, the major autolysin AtlL, and the type VII secretion system. Overall, our data suggest that the LytSR TCS is implicated in S. lugdunensis pathogenesis, through its involvement in biofilm formation and potentially by the control of genes encoding putative virulence factors.

中文翻译：

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LytSR 双组分调节系统在路邓葡萄球菌生物膜形成和发病机制中的作用。


路邓葡萄球菌是一种凝固酶阴性葡萄球菌，被认为是一种剧毒病原体。它导致多种感染，其中一些与生物膜的产生有关，例如植入医疗设备感染或心内膜炎。然而，人们对路邓链球菌毒力因子表达的调节知之甚少。双组分调节系统 (TCS) 在细菌适应、生存和毒力方面发挥着关键作用。其中，LytSR 广泛保守，但在不同生物体中具有不同的作用，所有这些都与生物膜发育过程中发生的代谢或细胞死亡和裂解有关。因此，我们在此研究了 LytSR 在路邓沙门氏菌发病机制中的功能。路邓沙门氏菌 DSM 4804 菌株中 lytSR 的缺失不会改变对 Triton X-100 诱导的自溶的敏感性，也不会改变针对细胞壁合成的抗生素诱导的死亡。有趣的是，与野生型菌株相比，ΔlytSR生物膜的特点是生物量较低、缺乏塔结构和死细胞率较高。与野生型菌株相比，使用慢杀试验，突变体对秀丽隐杆线虫的毒力显着降低。相比之下，lytSR的缺失对路邓沙门氏菌对人角质形成细胞系HaCaT的细胞毒性没有影响。在指数中期和后期进行的转录分析表明，lytSR 缺失影响了 286 个基因的表达。其中大多数涉及氨基酸、碳水化合物和核苷酸的代谢等基本功能。 此外，LytSR 似乎参与编码已知或推定毒力和定植因子的基因的调节，包括纤维蛋白原结合蛋白 Fbl、主要自溶素 AtlL 和 VII 型分泌系统。总体而言，我们的数据表明，LytSR TCS 通过参与生物膜形成并可能通过控制编码假定毒力因子的基因，与路邓沙门氏菌发病机制有关。