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Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

OT-CATH, a conserved antimicrobial peptide in Otariidae species, exhibits potent activity against gram-negative bacteria

  • Yixiao Song1,2
  • Yufeng Ren1,2
  • Juan Wang1,3
  • Zifan Ye1,4
  • Chenchen Shi1,2
  • Xiangjin Kong1,2
  • Xudong Jiao1,2
  • Jingjing Zhang1,2
  • Yipeng Wang1,2
4 affiliations
  1. 1Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, China
  2. 2University of Chinese Academy of Sciences, Beijing, China
  3. 3Research Institute of Marine Traditional Chinese Medicine (Qingdao Academy of Chinese Medical Sciences), Shandong University of Traditional Chinese Medicine, Qingdao, China
  4. 4Department of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China
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Abstract

The rapid emergence of multidrug-resistant gram-negative bacteria necessitates the development of effective antimicrobial agents to combat antimicrobial resistance. Here, we identified and characterized OT-CATH, a conserved cathelicidin-family antimicrobial peptide derived from Otariidae species. OT-CATH exhibited potent bactericidal activity against gram-negative bacteria, particularly extended-spectrum β-lactamase-producing Escherichia coli, with rapid killing kinetics, potent antibiofilm activity, and no detectable resistance after 40 serial passages. Mechanistically, OT-CATH bound lipopolysaccharide, disrupted both the outer and inner bacterial membranes, and translocated into the cytoplasm to interact with bacterial DNA. Membrane disruption further triggered intracellular reactive oxygen species accumulation, proton motive force dissipation, ATP depletion, and metabolic collapse, collectively leading to bacterial death. OT-CATH also demonstrated favorable stability, low cytotoxicity, and favorable pharmacokinetic properties with measurable pulmonary distribution. In a murine pneumonia model, OT-CATH significantly improved survival, reduced bacterial burdens in the lungs and bronchoalveolar lavage fluid, and alleviated lung injury. These findings identify OT-CATH as a promising membrane-targeting antimicrobial peptide for the treatment of multidrug-resistant gram-negative bacterial infections.

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Cite

BibTeXRIS
BibTeX
@article{song2026otcath,
  title = {{OT-CATH, a conserved antimicrobial peptide in Otariidae species, exhibits potent activity against gram-negative bacteria}},
  author = {Yixiao Song and Yufeng Ren and Juan Wang and Zifan Ye and Chenchen Shi and Xiangjin Kong and Xudong Jiao and Jingjing Zhang and Yipeng Wang},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = oct,
  doi = {10.1128/aac.01026-26},
  url = {https://doi.org/10.1128/aac.01026-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - OT-CATH, a conserved antimicrobial peptide in Otariidae species, exhibits potent activity against gram-negative bacteria
AU  - Yixiao Song
AU  - Yufeng Ren
AU  - Juan Wang
AU  - Zifan Ye
AU  - Chenchen Shi
AU  - Xiangjin Kong
AU  - Xudong Jiao
AU  - Jingjing Zhang
AU  - Yipeng Wang
PY  - 2026
DA  - 2026/10/01
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.01026-26
UR  - https://doi.org/10.1128/aac.01026-26
AB  - The rapid emergence of multidrug-resistant gram-negative bacteria necessitates the development of effective antimicrobial agents to combat antimicrobial resistance. Here, we identified and characterized OT-CATH, a conserved cathelicidin-family antimicrobial peptide derived from Otariidae species. OT-CATH exhibited potent bactericidal activity against gram-negative bacteria, particularly extended-spectrum β-lactamase-producing Escherichia coli, with rapid killing kinetics, potent antibiofilm activity, and no detectable resistance after 40 serial passages. Mechanistically, OT-CATH bound lipopolysaccharide, disrupted both the outer and inner bacterial membranes, and translocated into the cytoplasm to interact with bacterial DNA. Membrane disruption further triggered intracellular reactive oxygen species accumulation, proton motive force dissipation, ATP depletion, and metabolic collapse, collectively leading to bacterial death. OT-CATH also demonstrated favorable stability, low cytotoxicity, and favorable pharmacokinetic properties with measurable pulmonary distribution. In a murine pneumonia model, OT-CATH significantly improved survival, reduced bacterial burdens in the lungs and bronchoalveolar lavage fluid, and alleviated lung injury. These findings identify OT-CATH as a promising membrane-targeting antimicrobial peptide for the treatment of multidrug-resistant gram-negative bacterial infections.
SN  - 1098-6596
SN  - 0066-4804
ER  -