Department of Laboratory Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Commun Biol. 2022 Jun 23;5(1):618. doi: 10.1038/s42003-022-03571-x.
Pneumonia caused by community-associated Staphylococcus aureus (CA-SA) has high morbidity and mortality, but its pathogenic mechanism remains to be further investigated. Herein, we identify that staphylokinase (SAK) is significantly induced in CA-SA and inhibits biofilm formation in a plasminogen-dependent manner. Importantly, SAK can enhance CA-SA-mediated pneumonia in both wild-type and cathelicidins-related antimicrobial peptide knockout (CRAMP) mice, suggesting that SAK exacerbates pneumonia in a CRAMP-independent manner. Mechanistically, SAK induces pro-inflammatory effects, especially in the priming step of NLRP3 inflammasome activation. Moreover, we demonstrate that SAK can increase K efflux, production of reactive oxygen species production, and activation of NF-κB signaling. Furthermore, the NLRP3 inflammasome inhibitor can counteract the effective of SAK induced CA-SA lung infection in mice. Taken together, we speculate that SAK exacerbates CA-SA-induced pneumonia by promoting NLRP3 inflammasome activation, providing new insights into the pathogenesis of highly virulent CA-SA and emphasizes the importance of controlling inflammation in acute pneumonia.
社区相关性金黄色葡萄球菌（CA-SA）引起的肺炎发病率和死亡率很高，但致病机制仍有待进一步研究。在此，我们发现金葡菌激酶（SAK）在 CA-SA 中显著诱导，并以纤溶酶原依赖的方式抑制生物膜形成。重要的是，SAK 可增强野生型和抗菌肽相关 cathelicidins 缺失型（CRAMP）小鼠中 CA-SA 介导的肺炎，提示 SAK 以 CRAMP 非依赖性方式加重肺炎。机制上，SAK 诱导促炎作用，特别是在 NLRP3 炎性体激活的初始步骤。此外，我们证明 SAK 可增加 K+外流、活性氧的产生和 NF-κB 信号通路的激活。此外，NLRP3 炎性体抑制剂可拮抗 SAK 诱导的 CA-SA 肺部感染在小鼠中的作用。总之，我们推测 SAK 通过促进 NLRP3 炎性体激活来加重 CA-SA 诱导的肺炎，为高度毒性 CA-SA 的发病机制提供了新的见解，并强调控制急性肺炎炎症的重要性。
