Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
Int Immunopharmacol. 2022 Jul;108:108856. doi: 10.1016/j.intimp.2022.108856. Epub 2022 May 21.
Methicillin-resistant Staphylococcus aureus (MRSA) has an increasing prevalence of multi-drug resistance. There is an urgent need for developing novel approaches to combat MRSA infection. Mucosal pentraxin 2 (Mptx2) is predicted to be a member of the pentraxin family, but its biological function is still unknown. This study is aimed to explore the roles of Mptx2 in MRSA-associated peritoneal infection. The recombinant Mptx2 protein is used to evaluate its antibacterial activity. Biofilm formation assay and macrophage phagocytic experiment are performed to explore the involved mechanisms. The effects of Mptx2 on peritoneal infection are investigated in a MRSA-induced peritoneal infected model. We here show that addition of Mptx2 suppresses the growth and biofilm formation of MRSA in vitro. Enzyme-linked immunosorbent assay (ELISA) binding analysis shows that Mptx2 protein directly binds to the MRSA. Additionally, Mptx2 supplementation promotes macrophages to phagocytize and clear the MRSA. In the MRSA-infected peritonitis model, Mptx2 administration reduces MRSA loading in peritoneal organs and alleviates peritoneal damage. Mptx2 knockout aggravates MRSA infection-induced peritoneal injury. In conclusion, our findings reveal that Mptx2 has bactericidal activity against MRSA both in vitro and in vivo, which may shed light on the discovery and development of novel strategies for MRSA-infected peritonitis.
耐甲氧西林金黄色葡萄球菌(MRSA)的多药耐药性日益普遍。因此,迫切需要开发新的方法来对抗 MRSA 感染。黏膜五聚素 2(Mptx2)被预测为五聚素家族的一员,但它的生物学功能尚不清楚。本研究旨在探讨 Mptx2 在 MRSA 相关腹膜炎中的作用。使用重组 Mptx2 蛋白评估其抗菌活性。通过生物膜形成试验和巨噬细胞吞噬试验探讨其相关机制。在 MRSA 诱导的腹膜感染模型中研究 Mptx2 对腹膜感染的影响。我们在此表明,添加 Mptx2 可抑制 MRSA 在体外的生长和生物膜形成。酶联免疫吸附试验(ELISA)结合分析表明,Mptx2 蛋白可直接与 MRSA 结合。此外,Mptx2 补充可促进巨噬细胞吞噬和清除 MRSA。在 MRSA 感染性腹膜炎模型中,Mptx2 给药可减少腹膜器官中的 MRSA 载量并减轻腹膜损伤。Mptx2 敲除可加重 MRSA 感染诱导的腹膜损伤。总之,我们的研究结果表明,Mptx2 对 MRSA 具有体外和体内的杀菌活性,这可能为开发治疗 MRSA 感染性腹膜炎的新策略提供思路。