Hazam, Prakash KishorePrakash KishoreHazamCheng, Chih-ChengChih-ChengChengLin, Wen-ChunWen-ChunLinHsieh, Chu-YiChu-YiHsiehHsu, Po-HsienPo-HsienHsuChen, Yun-RuYun-RuChenLi, Chao-ChinChao-ChinLiPO-REN HSUEHChen, Jyh-YihJyh-YihChen2023-02-142023-02-142023-01-1802235234https://scholars.lib.ntu.edu.tw/handle/123456789/628086Antimicrobial 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.enAntimicrobial peptides (AMPs); Multidrug-resistant (MDR) bacteria; Murine wound infection model; Peptide drug design; Tilapia piscidins (TPs); Vibrio vulnificus[SDGs]SDG3journal article10.1016/j.ejmech.2023.115131366693992-s2.0-85146469947https://api.elsevier.com/content/abstract/scopus_id/85146469947