Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin

doi:10.1021/acsinfecdis.3c00575

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	Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin
	Cai, Ying; Wang, Xingyu; Zhang, Tianyu; Yan, An; Luo, Lin; Li, Chenxi; Tian, Gengzhou; Wu, Zhongxiang; Wang, Xi; Shen, Dong; Han, Yajun; Zhang, Zhiye
	2024
发表期刊	ACS INFECTIOUS DISEASES
ISSN	2373-8227
卷号	10 期号:3 页码:951-960
摘要	The emergence of multidrug-resistant (MDR) bacteria presents a significant challenge to public health, increasing the risk of infections that are resistant to current antibiotic treatment. Antimicrobial peptides (AMPs) offer a promising alternative to conventional antibiotics in the prevention of MDR bacterial infections. In the present study, we identified a novel cathelicidin AMP from Gekko japonicus, which exhibited broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with minimal inhibitory concentrations ranging from 2.34 to 4.69 mu g/mL. To improve its potential therapeutic application, a series of peptides was synthesized based on the active region of the gecko-derived cathelicidin. The lead peptide (RH-16) showed an antimicrobial activity comparable to that of the parent peptide. Structural characterization revealed that RH-16 adopted an amphipathic alpha-helical conformation. Furthermore, RH-16 demonstrated neither hemolytic nor cytotoxic activity but effectively killed a wide range of clinically isolated, drug-resistant bacteria. The antimicrobial activity of RH-16 was attributed to the nonspecific targeting of bacterial membranes, leading to rapid bacterial membrane permeabilization and rupture. RH-16 also retained its antibacterial activity in plasma and exhibited mild toxicity in vivo. Notably, RH-16 offered robust protection against skin infection in a murine model. Therefore, this newly identified cathelicidin AMP may be a strong candidate for future pharmacological development targeting multidrug resistance. The use of a rational design approach for isolating the minimal antimicrobial unit may accelerate the transition of natural AMPs to clinically applicable antibacterial agents.[GRAPHICS].
DOI	10.1021/acsinfecdis.3c00575
WOS记录号	WOS:001164442100001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/76255
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Cai, Ying,Wang, Xingyu,Zhang, Tianyu,et al. Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin[J]. ACS INFECTIOUS DISEASES,2024,10(3):951-960.
APA	Cai, Ying.,Wang, Xingyu.,Zhang, Tianyu.,Yan, An.,Luo, Lin.,...&Zhang, Zhiye.(2024).Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin.ACS INFECTIOUS DISEASES,10(3),951-960.
MLA	Cai, Ying,et al."Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin".ACS INFECTIOUS DISEASES 10.3(2024):951-960.

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