Strategic modification of low-activity natural antimicrobial peptides confers antibacterial potential in vitro and in vivo
Journal
European journal of medicinal chemistry
Journal Volume
249
Date Issued
2023-01-18
Author(s)
Hazam, Prakash Kishore
Cheng, Chih-Cheng
Lin, Wen-Chun
Hsieh, Chu-Yi
Hsu, Po-Hsien
Chen, Yun-Ru
Li, Chao-Chin
Chen, Jyh-Yih
Abstract
Antimicrobial peptides (AMPs) show great promise for clinical applications, but the utility of naturally occurring AMPs is often limited by their stability. Here, we used a rational design approach to improve the characteristics of a pair of inactive peptides, tilapia piscidin 1 and 2 (TP1 and TP2). From each starting peptide, we generated a series of novel derivatives by substituting residues to adjust cationic charge density, percent hydrophobicity and hydrophilicity/hydrophobicity coefficients. This approach yielded a novel peptide, TP2-5 (KKCIAKAILKKAKKLLKKLVNP), that exhibits significant bactericidal potency, low cytotoxicity and high stability. The designed peptide further showed antibiofilm activity, rapid antibacterial action and a low capacity to induce bacterial resistance. Importantly, we also demonstrated that TP2-5 can protect mice in a Vibrio vulnificus-infected wound model. Therefore, our peptide modification strategy successfully generated a novel AMP with high potential for future clinical application.
Subjects
Antimicrobial peptides (AMPs); Multidrug-resistant (MDR) bacteria; Murine wound infection model; Peptide drug design; Tilapia piscidins (TPs); Vibrio vulnificus
SDGs
Type
journal article