The Small RNA Teg41 Is a Pleiotropic Regulator of Virulence in Staphylococcus aureus [wt teg41]

Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (aPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the aPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41?3' strain is more severely attenuated in two murine infection models than a ?aPSM strain, indicating that Teg41 regulation reaches beyond the aPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes. Overall design: 18 datasets in total. Two strains (wild type and Teg41D3' strain) grown to three timepoints (3, 6, 9 h), with three replicates for each strain at each timepoint.

金黄色葡萄球菌（Staphylococcus aureus）是革兰氏阳性（Gram-positive）共生菌，同时可引发人类疾病，病症谱涵盖轻症、可自愈的皮肤感染，乃至心内膜炎、骨髓炎、败血症等致命病症。此前我们已证实，金黄色葡萄球菌的小RNA（sRNA）Teg41可调控α-苯酚可溶性调控毒素（alpha Phenol Soluble Modulin toxins，aPSMs）的生成。本研究中，我们进一步解析了Teg41的调控功能。RNA测序（RNAseq）分析显示，与野生型金黄色葡萄球菌相比，Teg41不仅可影响aPSM转录本的丰度，还可调控多种其他转录本的水平。蛋白质组学分析证实，敲除细胞内的Teg41会改变金黄色葡萄球菌的胞质蛋白与分泌蛋白谱。最后，我们观察到，相较于aPSM缺失菌株，Teg41 3'端缺失菌株在两种小鼠感染模型中的致病力衰减更为显著，这表明Teg41的调控范围不止于aPSMs。综上，我们证实Teg41是金黄色葡萄球菌中一种独特的多效性sRNA，可调控多项关键细胞进程。实验整体设计：共计18组数据集。选取两种菌株（野生型菌株与Teg41 3'端缺失菌株），培养至3个时间节点（3、6、9小时），每个菌株在每个时间节点下设置3次生物学重复。