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Bat-Derived Antimicrobial Peptide MC-CATH3 Confers Protection Against Bacterial Infections via a Potential
Xiangjin Kong1, Zhouye Xu2, Jinhui Li3
1Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences; Yantai, Shandong 264003, China; University of Chinese Academy of Sciences; Beijing 100049, China.
Abstract:
Most naturally occurring antimicrobial peptides (AMPs) exert bactericidal activity by disrupting bacterial membranes, and although alternative mechanisms have been described, AMPs associated with ferroptosis-like features in bacterial killing remain rare. Here, we identified three novel AMPs, MC-CATH1-3, from the bat Myotis chinensis. All three peptides adopt an α-helical conformation and display potent antimicrobial activity. Notably, compared with MC-CATH1/2, MC-CATH3 causes weak membrane perturbation but triggers metabolic imbalance and excessive production of reactive oxygen species, accompanied by iron-sulfur cluster damage and abnormal intracellular Fe2+ accumulation. These events are associated with Fenton reaction-driven lipid peroxidation and are consistent with a potential ferroptosis-like bacterial death process. In vivo, MC-CATHs, especially MC-CATH3, exhibit remarkable therapeutic efficacy in cutaneous wound infection. Collectively, our findings broaden the conceptual framework of AMP mechanisms and suggest that MC-CATH3 may serve as a promising template for the rational design of peptide antibiotics with novel modes of action.
Insights
Researchers discovered novel antimicrobial peptides (AMPs) from bats. One peptide, MC-CATH3, kills bacteria via a ferroptosis-like process, offering a new strategy for antibiotic development.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Antimicrobial peptides (AMPs) are crucial in innate immunity.
- Most AMPs kill bacteria by disrupting cell membranes.
- Alternative bacterial killing mechanisms, especially ferroptosis-like pathways, are less understood.
Purpose of the Study:
- To identify and characterize novel AMPs from the bat Myotis chinensis.
- To investigate the mechanism of action of these AMPs, particularly focusing on ferroptosis-like features.
- To evaluate the therapeutic potential of these AMPs in vivo.
Main Methods:
- Isolation and purification of antimicrobial peptides from bat venom.
- Determination of peptide structure (α-helical conformation).
- Assessment of antimicrobial activity, membrane perturbation, reactive oxygen species (ROS) production, iron accumulation, and lipid peroxidation.
- In vivo testing in a murine model of cutaneous wound infection.
Main Results:
- Three novel AMPs, MC-CATH1-3, were identified, all exhibiting antimicrobial activity.
- MC-CATH3 induced bacterial death through metabolic imbalance, excessive ROS production, iron-sulfur cluster damage, and Fe2+ accumulation, indicative of ferroptosis.
- MC-CATH3 showed significant therapeutic efficacy in treating bacterial skin infections in vivo.
Conclusions:
- The study broadens the understanding of AMP mechanisms beyond membrane disruption.
- MC-CATH3 represents a novel class of AMPs that induce bacterial ferroptosis.
- MC-CATH3 serves as a promising lead for developing new peptide antibiotics with unique modes of action.
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