Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus.
Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus.
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DOI：
10.1128/msphere.00676-21
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发表时间：
2021-10-27
期刊：
影响因子：
4.8
通讯作者：
Carroll RK
中科院分区：
文献类型：
--
作者：
Briaud P;Frey A;Marino EC;Bastock RA;Zielinski RE;Wiemels RE;Keogh RA;Murphy ER;Shaw LN;Carroll RK
金黄色葡萄球菌是一种致病性细菌，也是人体皮肤和前鼻孔的寄生虫。作为S.金黄色葡萄球菌从皮肤/鼻孔进入人体内部，它会经历温度的变化。研究了S.金黄色葡萄球菌细胞外囊泡（EV）在过去几年中得到越来越多的研究，并且EV越来越被认为对感染过程是重要的。尽管如此，温度变化对S。金黄色葡萄球菌EV尚未详细研究，因为大多数研究EV货物和宿主细胞相互作用的报告都是使用在37°C下产生的囊泡进行的。在这里，我们报告说，电动汽车在S。金黄色葡萄球菌的大小和蛋白质/RNA货物不同，这取决于所使用的生长温度。我们证明，温度依赖性调节囊泡的生产在S。金黄色葡萄球菌是由α酚可溶性调节肽（α PSM）介导的。通过蛋白质组学分析，我们观察到在40°C下毒力因子的包装增加，而EV蛋白质组在34°C下具有更大的多样性。与蛋白质含量类似，我们进行了转录组学分析，并证明RNA货物也受到温度的影响。最后，我们证明了40°C EV的αPSM和α毒素介导的红细胞溶解更大，但34°C EV对THP-1细胞的细胞毒性更强。总之，我们的研究表明，小的温度变化对EV生物发生有很大的影响，并形成与宿主细胞的相互作用。细胞外囊泡（EV）是含有蛋白质、核酸和由细菌分泌的脂质的脂质双层球体。它们参与金黄色葡萄球菌感染，因为它们包装毒力因子并将其内容物递送到宿主细胞内。温度变化对S.金黄色葡萄球菌在EV感染过程中的作用尚不清楚。在这里，我们证明了温度在囊泡生产和包装中的重要性。高温会促进毒力因子的包装，增加蛋白质和脂质浓度，但会降低EV中的总体RNA丰度和蛋白质多样性。温度变化的重要性通过以下事实突出：在低温下产生的EV对巨噬细胞更具毒性，而在高温下产生的EV对红细胞显示出更多的溶血。我们的研究为S.金黄色葡萄球菌从定植到毒力的转变。
Staphylococcus aureus is a pathogenic bacterium but also a commensal of skin and anterior nares in humans. As S. aureus transits from skins/nares to inside the human body, it experiences changes in temperature. The production and content of S. aureus extracellular vesicles (EVs) have been increasingly studied over the past few years, and EVs are increasingly being recognized as important to the infectious process. Nonetheless, the impact of temperature variation on S. aureus EVs has not been studied in detail, as most reports that investigate EV cargoes and host cell interactions are performed using vesicles produced at 37°C. Here, we report that EVs in S. aureus differ in size and protein/RNA cargo depending on the growth temperature used. We demonstrate that the temperature-dependent regulation of vesicle production in S. aureus is mediated by the alpha phenol-soluble modulin peptides (αPSMs). Through proteomic analysis, we observed increased packaging of virulence factors at 40°C, whereas the EV proteome has greater diversity at 34°C. Similar to the protein content, we perform transcriptomic analysis and demonstrate that the RNA cargo also is impacted by temperature. Finally, we demonstrate greater αPSM- and alpha-toxin-mediated erythrocyte lysis with 40°C EVs, but 34°C EVs are more cytotoxic toward THP-1 cells. Together, our study demonstrates that small temperature variations have great impact on EV biogenesis and shape the interaction with host cells. IMPORTANCE Extracellular vesicles (EVs) are lipid bilayer spheres that contain proteins, nucleic acids, and lipids secreted by bacteria. They are involved in Staphylococcus aureus infections, as they package virulence factors and deliver their contents inside host cells. The impact of temperature variations experienced by S. aureus during the infectious process on EVs is unknown. Here, we demonstrate the importance of temperature in vesicle production and packaging. High temperatures promote packaging of virulence factors and increase the protein and lipid concentration but reduce the overall RNA abundance and protein diversity in EVs. The importance of temperature changes is highlighted by the fact that EVs produced at low temperature are more toxic toward macrophages, whereas EVs produced at high temperature display more hemolysis toward erythrocytes. Our research brings new insights into temperature-dependent vesiculation and interaction with the host during S. aureus transition from colonization to virulence.