Although bactericidal cationic antimicrobial peptides (AMPs) have been well characterized, less information is available about the antibacterial properties and mechanisms of action of nonbactericidal AMPs, especially nonbactericidal anionic AMPs. Herein, a novel anionic antimicrobial peptide (Gy-CATH) with a net charge of −4 was identified from the skin of the frog Glyphoglossus yunnanensis. Gy-CATH lacks direct antibacterial effects but exhibits significantly preventive and therapeutic capacities in mice that are infected with Staphylococcus aureus, Enterobacteriaceae coli, methicillin-resistant Staphylococcus aureus (MRSA), or carbapenem-resistant E. coli (CREC). In vitro and in vivo investigations proved the regulation of Gy-CATH on neutrophils and macrophages involved in the host immune defense against infection. Moreover, Gy-CATH significantly reduced the extent of pulmonary fibrin deposition and prevented thrombosis in mice, which was attributed to the regulatory role of Gy-CATH in physiological anticoagulants and platelet aggregation. These findings show that Gy-CATH is a potential candidate for the treatment of bacterial infection.

中文翻译：

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非杀菌性阴离子抗菌肽通过免疫调节-抗血栓二元性对小鼠细菌感染提供预防和治疗功效

尽管杀菌性阳离子抗菌肽 (AMP) 已得到很好的表征，但有关非杀菌性 AMP（尤其是非杀菌性阴离子 AMP）的抗菌特性和作用机制的信息较少。在此，从青蛙Glyphoglossus yunnanensis的皮肤中鉴定出一种净电荷为 -4 的新型阴离子抗菌肽（Gy-CATH）。 Gy-CATH缺乏直接抗菌作用，但对感染金黄色葡萄球菌、肠杆菌、耐甲氧西林金黄色葡萄球菌（MRSA）或耐碳青霉烯类大肠杆菌（CREC）的小鼠表现出显着的预防和治疗能力。体外和体内研究证明 Gy-CATH 对中性粒细胞和巨噬细胞的调节作用参与宿主针对感染的免疫防御。此外，Gy-CATH 显着降低小鼠肺纤维蛋白沉积程度并防止血栓形成，这归因于 Gy-CATH 对生理抗凝和血小板聚集的调节作用。这些发现表明 Gy-CATH 是治疗细菌感染的潜在候选药物。