Integrating a cationic backbone with a hydrophobic core: A structure-function strategy for designing self-assembling antimicrobial peptides with enhanced activity

	Integrating a cationic backbone with a hydrophobic core: A structure-function strategy for designing self-assembling antimicrobial peptides with enhanced activity
	Mwangi, J; Tadese, DA; Wang, Y; Asmamaw, D; Yang, M; Michira, BB; Khalid, M; Wang, ZY; Lu, QM; Lai, R
	2025
发表期刊	Zool. Res.
ISSN	2095-8137
卷号	46 期号:5 页码:1203-1218
摘要	Effective countermeasures against multidrug-resistant nosocomial pathogens, such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA), require the development of innovative antimicrobial strategies. This study presents a structure-function approach to antimicrobial peptide (AMP) design through the strategic integration of a cationic backbone with a hydrophobic core. This dual-domain architecture enables robust hydrophobic and electrostatic interactions, promoting spontaneous self-assembly and efficient membrane engagement. The lead peptide, Tryptolycin (TRPY), formed stable, monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity, with minimum inhibitory concentrations <= 1 mu M against multiple strains of MRSA and K. pneumoniae, while exerting minimal cytotoxicity toward mammalian cells. TRPY achieved rapid bacterial elimination, eradicating 99.9% of both planktonic and persister populations within minutes. Mechanistic investigations revealed that TRPY induced membrane permeabilization, promoted reactive oxygen species (ROS) production, and inhibited biofilm formation. In murine infection models, TRPY effectively eradicated established infections, reducing bacterial burden across target organs by 3-to 5-fold without significant cytotoxicity at therapeutic concentrations. Collectively, these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14842
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Mwangi, J,Tadese, DA,Wang, Y,et al. Integrating a cationic backbone with a hydrophobic core: A structure-function strategy for designing self-assembling antimicrobial peptides with enhanced activity[J]. Zool. Res.,2025,46(5):1203-1218.
APA	Mwangi, J.,Tadese, DA.,Wang, Y.,Asmamaw, D.,Yang, M.,...&Lai, R.(2025).Integrating a cationic backbone with a hydrophobic core: A structure-function strategy for designing self-assembling antimicrobial peptides with enhanced activity.Zool. Res.,46(5),1203-1218.
MLA	Mwangi, J,et al."Integrating a cationic backbone with a hydrophobic core: A structure-function strategy for designing self-assembling antimicrobial peptides with enhanced activity".Zool. Res. 46.5(2025):1203-1218.

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2026070621.pdf（13709KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文