ResearchApr 4, 20260 views

Bacterial terminal oxidase bo(3) as a primary respiratory target of cathelicidin peptide hc-cath against Acinetobacter baumannii.

Cathelicidin peptides just leveled up in the antimicrobial playbook. Researchers gave Acinetobacter baumannii—the hospital superbug—something new to worry about: a sea snake-derived cathelicidin called hc-cath. The headline? Hc-cath doesn’t just poke holes in bacterial membranes. It targets the bacteria’s core respiratory machinery, specifically the terminal oxidase bo(3).

J Adv Res

by Wang Y, Zhou S, Su D et al.

“Bacterial terminal oxidase bo(3) as a primary respiratory target of cathelicidin peptide hc-cath against Acinetobacter baumannii. Wang Y(1), Zhou S(2), Su D(3), Song Z(4), Chen Y(2), Mwangi J(2), Lv Q(2), Wang A(5), Lai R(6). Author information: (1)Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China. (2)Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, Yunnan, China; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, China; University of Chinese Academy of Sciences, Beijing 100049, China. (3)Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, Yunnan, China; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, China. (4)School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China. (5)Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China. Electronic address: allie612@gmlab.ac.cn. (6)Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China; Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, Yunnan, China. Electronic address: rlai@mail.kiz.ac.cn. INTRODUCTION: Antimicrobial peptides (AMPs) hold promises to counter antimicrobial resistance. They cause several deleterious effects in bacterial cells by interfering with cell wall biosynthesis, DNA replication, transcription, and translation. OBJECTIVES: The essential role of cellular respiration in bacterial survival underscores its potential as a target for antimicrobial intervention. However, few studies have explored if and how AMPs target bacterial respiratory terminal oxidases, which contribute to proton motive force (PMF) for ATP synthesis and are essential for cell survival. METHODS: In vitro and in vivo experiments are performed to examine the antimicrobial activities of hc-cath, the first sea snake-derived cathelicidin peptide, against A. baumannii. Mode of action (MOA) of hc-cath is confirmed through a series of biochemical, enzymatic, and biophysical assays along with transcriptome analysis. RESULTS: In this investigation, hc-cath is found to interact with and inhibit the terminal oxidase bo3 in A. baumannii, disrupting PMF and inducing toxic reactive oxygen species (ROS) production. Mitigating oxidative stress rescues bacterial death induced by hc-cath. Phenotypic validation using a cyoB (encoding oxidase bo3)-deficient strain further confirms the reduced peptide susceptibility and attenuates respiratory metabolic perturbation. CONCLUSION: Our research identifies oxidase bo3, which predominates under high aeration growth conditions, as a key potential target of AMPs, underscoring bacterial respiratory metabolism as a viable therapeutic focus for AMPs-based strategies. Copyright © 2026 The Author(s). Published by Elsevier B.V. All rights reserved. Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”

Here’s what matters. Terminal oxidase bo(3) is crucial for A. baumannii’s energy production. Researchers showed that hc-cath binds to and inhibits this enzyme, short-circuiting the bacteria’s proton motive force. The result: ATP production tanks and toxic reactive oxygen species (ROS) pile up. That’s a one-two punch—starving the cell of energy and flooding it with oxidative stress.

Key takeaway:

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Cathelicidins like hc-cath can hit bacteria where they breathe, not just where they bleed

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Disruption of oxidase bo(3) leads to bacterial death via energy collapse and ROS overload

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Bacteria missing the bo(3) enzyme are less affected by hc-cath, confirming the target

This is a shift for peptide research. Instead of thinking about antimicrobial peptides (AMPs) as generic membrane disruptors, researchers now have a precise molecular target in A. baumannii’s respiratory chain. This could guide new strategies for designing AMPs that exploit bacterial metabolism, not just their cell walls.

For anyone sourcing research peptides or designing experiments, this study shows why it’s worth looking beyond traditional mechanisms. The field is wide open for targeting respiratory enzymes in multi-drug resistant bacteria. Check out our vendor directory if you’re planning your own experiments.

Bottom line: Cathelicidin peptides like hc-cath are rewriting the rules on how AMPs can take down persistent pathogens. This is a win for the entire research community.

Back to News Read original on J Adv Res

Bacterial terminal oxidase bo(3) as a primary respiratory target of cathelicidin peptide hc-cath against Acinetobacter baumannii.

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