2. Academic Validation
  3. TC-14, a cathelicidin-derived antimicrobial peptide with broad-spectrum antibacterial activity and high safety profile

TC-14, a cathelicidin-derived antimicrobial peptide with broad-spectrum antibacterial activity and high safety profile

  • iScience. 2024 Jun 28;27(7):110404. doi: 10.1016/j.isci.2024.110404.
Chenxi Li 1 2,  Ying Cai 1,  Lin Luo 1 2,  Gengzhou Tian 3,  Xingyu Wang 1 4,  An Yan 1,  Liunan Wang 1,  Sijing Wu 1 4,  Zhongxiang Wu 1,  Tianyu Zhang 1,  Wenlin Chen 2,  Zhiye Zhang 1
Affiliations

Affiliations

  • 1 Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650031, Yunnan, China.
  • 2 Third Department of Breast Surgery, Peking University Cancer Hospital Yunnan, Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming 650118, Yunnan, China.
  • 3 Department of Breast Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
  • 4 School of Life Sciences, Yunnan University, Kunming 650500, China.
PMID: 39092176 DOI: 10.1016/j.isci.2024.110404
Abstract

Cathelicidins, a major class of antimicrobial peptides (AMPs), hold considerable potential for antimicrobial drug development. In the present study, we identified a novel cathelicidin AMP (TC-33) derived from the Chinese tree shrew. Despite TC-33 demonstrating weak antimicrobial activity, the novel peptide TC-14, developed based on its active region, exhibited a 432-fold increase in antimicrobial activity over the parent peptide. Structural analysis revealed that TC-14 adopted an amphipathic α-helical conformation. The bactericidal mechanism of TC-14 involved targeting and disrupting the Bacterial membrane, leading to rapid membrane permeabilization and rupture. Furthermore, TC-14 exhibited a high-safety profile, as evidenced by the absence of cytotoxic and hemolytic activities, as well as high biocompatibility and safety in vivo. Of note, its potent antimicrobial activity provided significant protection in a murine model of skin Infection. Overall, this study presents TC-14 as a promising drug candidate for antimicrobial drug development.

Keywords

bacteriology; microbiology; molecular biology.

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