Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cell Host Microbe. 2021 Jun 9;29(6):930-940.e4. doi: 10.1016/j.chom.2021.03.007. Epub 2021 Apr 13.
Staphylococcus aureus commonly infects the skin, but the host-pathogen interactions controlling bacterial growth remain unclear. S. aureus virulence is regulated by the Agr quorum-sensing system that controls factors including phenol-soluble modulins (PSMs), a group of cytotoxic peptides. We found a differential requirement for Agr and PSMα for pathogen growth in the skin. In neutrophil-deficient mice, S. aureus growth on the epidermis was unaffected, but the pathogen penetrated the dermis through mechanisms that require PSMα. In the dermis, pathogen expansion required Agr in wild-type mice, but not in neutrophil-deficient mice. Agr limited oxidative and non-oxidative killing in neutrophils by inhibiting pathogen late endosome localization and promoting phagosome escape. Unlike Agr, the SaeR/S virulence program was dispensable for growth in the epidermis and promoted dermal pathogen expansion independently of neutrophils. Thus, S. aureus growth and invasion are differentially regulated with Agr limiting intracellular killing within neutrophils to promote pathogen expansion in the dermis and subcutaneous tissue.
金黄色葡萄球菌通常感染皮肤，但控制细菌生长的宿主-病原体相互作用仍不清楚。金黄色葡萄球菌的毒力受 Agr 群体感应系统调节，该系统控制包括酚可溶性调节素 (PSM) 在内的多种细胞毒性肽。我们发现 Agr 和 PSMα 对皮肤中病原体生长的需求存在差异。在中性粒细胞缺陷小鼠中，金黄色葡萄球菌在表皮上的生长不受影响，但病原体通过需要 PSMα 的机制穿透真皮。在真皮中，野生型小鼠中病原体的扩张需要 Agr，但在中性粒细胞缺陷小鼠中则不需要。Agr 通过抑制病原体晚期内体定位和促进吞噬体逃逸来限制中性粒细胞中的氧化和非氧化杀伤。与 Agr 不同，SaeR/S 毒力程序对于表皮中的生长是可有可无的，并且独立于中性粒细胞促进真皮中病原体的扩张。因此，金黄色葡萄球菌的生长和入侵受到不同程度的调节，Agr 限制中性粒细胞内的细胞杀伤，以促进病原体在真皮和皮下组织中的扩张。
