Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides

Zifan Ye, Lei Fu, Shuangyu Li, Ziying Chen, Jianhong Ouyang, Xinci Shang, Yanli Liu, Lianghui Gao () and Yipeng Wang ()
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Zifan Ye: Soochow University
Lei Fu: Beijing Normal University
Shuangyu Li: Soochow University
Ziying Chen: Beijing Normal University
Jianhong Ouyang: Soochow University
Xinci Shang: Soochow University
Yanli Liu: Soochow University
Lianghui Gao: Beijing Normal University
Yipeng Wang: Soochow University

Nature Communications, 2024, vol. 15, issue 1, 1-26

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51730-x

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