Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Center for Clinical Laboratories, the Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Commun Biol. 2022 Sep 5;5(1):910. doi: 10.1038/s42003-022-03839-2.
Phenol-soluble modulin α (PSMα) is identified as potent virulence factors in Staphylococcus aureus (S. aureus) infections. Very little is known about the role of PSMβ which belongs to the same toxin family. Here we compared the role of PSMs in S. aureus-induced septic arthritis in a murine model using three isogenic S. aureus strains differing in the expression of PSMs (Newman, Δpsmα, and Δpsmβ). The effects of PSMs on neutrophil NADPH-oxidase activity were determined in vitro. We show that the PSMα activates neutrophils via the formyl peptide receptor (FPR) 2 and reduces their NADPH-oxidase activity in response to the phorbol ester PMA. Despite being a poor neutrophil activator, PSMβ has the ability to reduce the neutrophil activating effect of PSMα and to partly reverse the effect of PSMα on the neutrophil response to PMA. Mice infected with S. aureus lacking PSMα had better weight development and lower bacterial burden in the kidneys compared to mice infected with the parental strain, whereas mice infected with bacteria lacking PSMβ strain developed more severe septic arthritis accompanied with higher IL-6 and KC. We conclude that PSMα and PSMβ play distinct roles in septic arthritis: PSMα aggravates systemic infection, whereas PSMβ protects arthritis development.
酚可溶性调节素 α（PSMα）被鉴定为金黄色葡萄球菌（S. aureus）感染的强效毒力因子。关于属于同一毒素家族的 PSMβ的作用知之甚少。在这里，我们使用三种在 PSM 表达上不同的同源金黄色葡萄球菌菌株（Newman、Δpsmα和Δpsmβ）在小鼠模型中比较了 PSM 在金黄色葡萄球菌诱导的败血性关节炎中的作用。在体外测定了 PSM 对中性粒细胞 NADPH 氧化酶活性的影响。我们表明 PSMα 通过甲酰肽受体（FPR）2 激活中性粒细胞，并降低其对佛波酯 PMA 的 NADPH 氧化酶活性。尽管 PSMβ 是一种较差的中性粒细胞激活剂，但它具有降低 PSMα 对中性粒细胞激活作用的能力，并部分逆转 PSMα 对中性粒细胞对 PMA 反应的作用。与感染亲本株的小鼠相比，缺乏 PSMα 的金黄色葡萄球菌感染的小鼠体重增长更好，肾脏中的细菌负担更低，而缺乏 PSMβ 菌株的细菌感染的小鼠则发展出更严重的败血性关节炎，伴随着更高的 IL-6 和 KC。我们得出结论，PSMα 和 PSMβ 在败血性关节炎中发挥不同的作用：PSMα 加重全身感染，而 PSMβ 则保护关节炎的发展。
