可编程肽纳米纤维能够有效根除MRSA生物膜和控制感染

Programmable Peptide Nanofibers Enable Effective MRSA Biofilm Eradication and Infection Control.

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摘要(中文译文)

随着抗生素耐药菌株的迅速增加以及抗菌药物研发的停滞,亟需替代性解决方案。抗菌肽(antimicrobial peptides, AMPs)因其结构多样性和对病原体的广谱活性而成为有前景的治疗药物。这种多功能性在对抗耐药微生物方面尤为引人注目,例如耐甲氧西林金黄色葡萄球菌(MRSA),该菌以引起持续性和生物膜相关感染而闻名。在本研究中,我们设计了一系列富含色氨酸-精氨酸的抗菌肽,即DVFLGREEWWWWWWC(D6W)、DVFLGREEWWWRWWWC(D6W1R)和DVFLGREEWWRWWRWWC(D6W2R),专门靶向MRSA。DVFLG结构域赋予其对MRSA的选择性亲和力,而富含色氨酸和精氨酸的片段则促进细菌膜破坏。结构分析表明,这些肽采用α-螺旋或β-折叠构象的混合形式,并自发自组装成纤维状或寡聚超分子结构。在测试的三种肽中,D6W2R表现出最高的抗菌活性,这与分子动力学模拟中观察到的趋势一致。除了杀灭浮游细菌外,所形成的肽纳米纤维还能有效抑制生物膜形成并破坏已建立的生物膜。值得注意的是,其抗菌性能在生理和病理条件下均得以保持,同时对哺乳动物细胞表现出极低的毒性。这些结果表明,自组装肽能够编码针对MRSA的高效、选择性抗菌活性,尤其是针对生物膜相关感染。

Abstract

With antibiotic-resistant bacterial strains rapidly increasing and the development of antibacterial drugs stagnating, alternative solutions are urgently needed. Antimicrobial peptides (AMPs) have emerged as promising therapeutics due to their structural diversity and broad-spectrum activity against pathogens. This versatility is particularly attractive for combating drug-resistant organisms such as methicillin-resistant (MRSA), which is notorious for causing persistent and biofilm-related infections. In this study, we engineered a series of tryptophan-arginine-rich antimicrobial peptides, i.e., DVFLGREEWWWWWWC (D6W), DVFLGREEWWWRWWWC (D6W1R), and DVFLGREEWWRWWRWWC (D6W2R), specifically targeting . The DVFLG domain confers selective affinity toward , while tryptophan- and arginine-rich segments promote bacterial membrane disruption. Structural analysis reveals that these peptides adopt a mixture of α-helix or β-sheet conformations and spontaneously self-assemble into fibrillar or oligomeric supramolecular structures. Among the three peptides tested, D6W2R exhibited the highest antibacterial activity, consistent with trends observed in the molecular dynamics simulations. Beyond eradicating planktonic bacteria, the resulting peptide nanofibers effectively inhibit biofilm formation and disrupt established biofilms. Notably, their antibacterial performance is preserved under and conditions while exhibiting minimal toxicity toward mammalian cells. These results demonstrated that self-assembled peptides can encode potent, selective antibacterial activity against MRSA, especially against biofilm-related infections.

如何引用

AMA

Suchita Paul, Wei-Yu Wang, Yu-Chun Hsiao, Zong-Kai Jiang, Chia-Chen Wu, Te-Haw Wu, et al. Programmable Peptide Nanofibers Enable Effective MRSA Biofilm Eradication and Infection Control.. ACS applied bio materials. 2026; doi:10.1021/acsabm.6c00441.

APA

Suchita Paul, Wei-Yu Wang, Yu-Chun Hsiao, Zong-Kai Jiang, Chia-Chen Wu, Te-Haw Wu, et al (2026). Programmable Peptide Nanofibers Enable Effective MRSA Biofilm Eradication and Infection Control.. ACS applied bio materials. https://doi.org/10.1021/acsabm.6c00441

GB/T 7714

Suchita Paul, Wei-Yu Wang, Yu-Chun Hsiao, Zong-Kai Jiang, Chia-Chen Wu, Te-Haw Wu, et al. Programmable Peptide Nanofibers Enable Effective MRSA Biofilm Eradication and Infection Control.[J]. ACS applied bio materials, 2026 doi:10.1021/acsabm.6c00441.

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