Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Microbiol Spectr. 2024 May 2;12(5):e0390523. doi: 10.1128/spectrum.03905-23. Epub 2024 Mar 19.
() is a Gram-negative facultative anaerobe that has become an important cause of severe infections in humans, particularly in patients with cystic fibrosis. The development of efficacious methods or mendicants against is still needed. We previously reported that regenerating islet-derived family member 4 (Reg4) has bactericidal activity against Typhimurium, a Gram-negative flagellated bacterium. We herein explore whether Reg4 has bactericidal activity against . In the PAO1-chronic infection model, Reg4 significantly inhibits the colonization of PAO1 in the lung and subsequently ameliorates pulmonary inflammation and fibrosis. Reg4 recombinant protein suppresses the growth motility and biofilm formation capability of PAO1 . Mechanistically, Reg4 not only exerts bactericidal action via direct binding to the cell wall but also enhances the phagocytosis of alveolar macrophages in the host. Taken together, our study demonstrates that Reg4 may provide protection against -induced pulmonary inflammation and fibrosis via its antibacterial activity.IMPORTANCEChronic lung infection with is a leading cause of morbidity and mortality in patients with cystic fibrosis. Due to the antibiotic resistance of , antimicrobial peptides appear to be a potential alternative to combat its infection. In this study, we report an antimicrobial peptide, regenerating islet-derived 4 (Reg4), that showed killing activity against clinical strains of PAO1 and ameliorated PAO1-induced pulmonary inflammation and fibrosis. Experimental data also showed Reg4 directly bound to the bacterial cell membrane and enhanced the phagocytosis of host alveolar macrophages. Our presented study will be a helpful resource in searching for novel antimicrobial peptides that could have the potential to replace conventional antibiotics.
（）是一种革兰氏阴性兼性厌氧菌，已成为人类严重感染的重要原因，尤其是在囊性纤维化患者中。仍然需要开发针对 的有效方法或药物。我们之前报道过，再生胰岛衍生家族成员 4（Reg4）对革兰氏阴性鞭毛菌鼠伤寒沙门氏菌具有杀菌活性。我们在此探讨 Reg4 是否对 具有杀菌活性。在 PAO1 慢性感染模型中，Reg4 显著抑制了 PAO1 在肺部的定植，并随后改善了肺部炎症和纤维化。Reg4 重组蛋白抑制了 PAO1 的生长运动性和生物膜形成能力。从机制上讲，Reg4 不仅通过直接与 细胞壁结合发挥杀菌作用，还增强了宿主肺泡巨噬细胞的吞噬作用。总之，我们的研究表明，Reg4 可能通过其抗菌活性为 - 诱导的肺部炎症和纤维化提供保护。
囊性纤维化患者的肺部慢性感染是发病率和死亡率的主要原因。由于 的抗生素耐药性，抗菌肽似乎是对抗其感染的一种潜在替代方法。在这项研究中，我们报告了一种抗菌肽，再生胰岛衍生 4（Reg4），它对临床株 PAO1 表现出杀伤活性，并改善了 PAO1 诱导的肺部炎症和纤维化。实验数据还表明，Reg4 直接与细菌细胞膜结合，并增强了宿主肺泡巨噬细胞的吞噬作用。我们的研究将为寻找具有替代传统抗生素潜力的新型抗菌肽提供有益的资源。
