Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Nat Commun. 2024 Aug 25;15(1):7319. doi: 10.1038/s41467-024-51730-x.
Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.
非直接抗菌阳离子肽（NDACPs）是动物先天免疫系统的组成部分。但它们的功能及其与抗菌肽（AMPs）的关系尚不完全清楚。在这里，我们揭示了 AMP AW1 和 NDACP AW2 之间的协同相互作用，这两种肽在蛙类 Amolops wuyiensis 中共同表达。AW2 增强了 AW1 的体外和体内的抗菌活性，同时减轻了细菌耐药性的发展并根除了生物膜。AW1 和 AW2 协同破坏细菌膜，促进细胞摄取和 AW2 与细胞内靶标细菌基因组 DNA 的相互作用。同时，它们在细菌中引发 ROS 的产生，当达到阈值水平时导致细胞死亡。此外，我们证明 AMP 和 NDACP 之间的这种协同抗菌作用在多种动物物种中普遍存在。这些发现揭示了 AMP 和 NDACP 之间作为动物中广泛存在的抗菌免疫防御策略的强大且以前未知的相关性。
