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, Yipeng Wang
Author Information
  1. Zifan Ye: Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
  2. Lei Fu: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
  3. Shuangyu Li: Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
  4. Ziying Chen: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
  5. Jianhong Ouyang: Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
  6. Xinci Shang: Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
  7. Yanli Liu: Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China. ORCID
  8. Lianghui Gao: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China. lhgao@bnu.edu.cn. ORCID
  9. Yipeng Wang: Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China. yipengwang@suda.edu.cn. ORCID

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.

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Grants

  1. 32070439/National Natural Science Foundation of China (National Science Foundation of China)
  2. 22373011/National Natural Science Foundation of China (National Science Foundation of China)
  3. 22373011/National Natural Science Foundation of China (National Science Foundation of China)

MeSH Term

Animals
Antimicrobial Cationic Peptides
Biofilms
Antimicrobial Peptides
Anti-Bacterial Agents
Drug Synergism
Reactive Oxygen Species
Microbial Sensitivity Tests
Ranidae
Mice
Immunity, Innate
Drug Resistance, Bacterial

Chemicals

Antimicrobial Cationic Peptides
Antimicrobial Peptides
Anti-Bacterial Agents
Reactive Oxygen Species

Word Cloud

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