A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition

	A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition
	Mwangi, J; Asmamaw, D; Yang, M; Tadese, DA; Michira, BB; Wang, Y; Zhou, SW; Wang, G; Wang, ZY; Lu, QM; Lai, R
	2025
发表期刊	Small
ISSN	1613-6810
卷号	21 期号:44
摘要	Quorum sensing (QS) plays a crucial role in biofilm formation, virulence, and antibiotic resistance, making it an attractive target for combating multidrug-resistant pathogens. Here, self-assembling peptides are designed by incorporating amphiphilic monomers with distinct hydrophobic and hydrophilic termini to achieve optimal self-assembly dynamics and interaction with bacterial membranes. The lead peptide, SAP2-PEG, spontaneously forms nanoparticles that transform into fibrillar networks under membrane-mimicking conditions. The peptide exhibits potent antimicrobial activity against critical nosocomial pathogens at low micromolar concentrations and disrupts both pre-formed and nascent polymicrobial biofilms. Mechanistically, SAP2-PEG disrupts bacterial membranes while simultaneously inhibiting QS by downregulating key genes, including the las and rh1 systems in Pseudomonas aeruginosa, and the agr system components in Staphylococcus aureus, as validated through transcriptome analysis. Notably, the peptide showed effectiveness against polymicrobial biofilms in both wound and catheter-associated infections. In vivo, it significantly reduced P. aeruginosa lung and S. aureus systemic infection. These findings establish SAP2-PEG as a promising therapeutic candidate that combines direct antimicrobial action with QS disruption for combating biofilm-associated 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/152453/14840
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,Asmamaw, D,Yang, M,et al. A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition[J]. Small,2025,21(44).
APA	Mwangi, J.,Asmamaw, D.,Yang, M.,Tadese, DA.,Michira, BB.,...&Lai, R.(2025).A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition.Small,21(44).
MLA	Mwangi, J,et al."A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition".Small 21.44(2025).

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