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对痤疮丙酸杆菌感染具有治疗潜力的含色氨酸肽。

Trp-containing Peptides with Therapeutic Potential for Cutibacterium acnes Infection.

作者信息

Li Mengmiao, Liu Zhuyun, He Jialu, Jiang Jiahuan, Shang Dejing, Dong Weibing

机构信息

School of Life Science, Liaoning Normal University, Dalian, 116081, China.

Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, 116081, China.

出版信息

Probiotics Antimicrob Proteins. 2025 Sep 9. doi: 10.1007/s12602-025-10749-2.

DOI:10.1007/s12602-025-10749-2
PMID:40924367
Abstract

Cutibacterium acnes (C. acnes, formerly classified as Propionibacterium acnes) is a Gram-positive bacterium that contributes to the development of acne vulgaris, resulting in inflammation and pustule formation on the skin. In this study, we developed and synthesized a series of antimicrobial peptides (AMPs) that are derived from the skin secretion of Rana chensinensis. Screening by MIC assay, Trp-containing peptides had potent anti-bacterial activity against C. acnes. The effect of Trp-containing peptides on the morphology was detected by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The cell surface of C. acnes that was treated with Trp-containing peptides appeared rough and irregular. Further investigations into the peptides effects on cell membranes were conducted via zeta potential, Disc3(5) and Live/Dead assays. The results revealed that the AMPs bound to the cell surface, induced the disruption of the cell membranes and ultimately led to cell death. The leakage of cellular contents like nucleic acid, K and Ca also confirmed the membrane-damaging effect of Trp-containing peptides. In addition, Trp-containing peptides suppressed biofilm formation and disrupted mature biofilms of C. acnes. Among the Trp-containing peptides, I4WL5W with lowest cytotoxic effect displayed dual anti-bacterial and anti-inflammatory effects in acne mice; it decreased the bacterial load and inhibited the levels of TNF-α, IL-6 and IL-1β in the infected skin. This study demonstrated that Trp-containing peptides might be promising candidates for treating acne.

摘要

痤疮丙酸杆菌(C. acnes,以前归类为痤疮丙酸杆菌)是一种革兰氏阳性细菌,它会导致寻常痤疮的发展,在皮肤上引发炎症和脓疱形成。在本研究中,我们开发并合成了一系列源自中国林蛙皮肤分泌物的抗菌肽(AMPs)。通过MIC测定法筛选,含色氨酸的肽对痤疮丙酸杆菌具有强大的抗菌活性。通过扫描电子显微镜(SEM)和原子力显微镜(AFM)检测含色氨酸的肽对其形态的影响。用含色氨酸的肽处理后的痤疮丙酸杆菌细胞表面显得粗糙且不规则。通过zeta电位、Disc3(5)和死活测定法对这些肽对细胞膜的影响进行了进一步研究。结果表明,这些抗菌肽与细胞表面结合,诱导细胞膜破裂并最终导致细胞死亡。细胞内容物如核酸、钾和钙的泄漏也证实了含色氨酸的肽对膜的破坏作用。此外,含色氨酸的肽抑制了痤疮丙酸杆菌的生物膜形成并破坏了其成熟生物膜。在含色氨酸的肽中,细胞毒性最低的I4WL5W在痤疮小鼠中显示出双重抗菌和抗炎作用;它降低了细菌载量并抑制了感染皮肤中TNF-α、IL-6和IL-1β的水平。这项研究表明,含色氨酸的肽可能是治疗痤疮的有前途的候选药物。

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本文引用的文献

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The antibacterial activity and mechanisms of Trp-containing peptides against multidrug-resistant Pseudomonas aeruginosa persisters.含色氨酸的肽类对多药耐药铜绿假单胞菌持续感染的抗菌活性及作用机制。
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Immune niches for hair follicle development and homeostasis.毛囊发育和稳态的免疫微环境。
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Macrophages in acne vulgaris: mediating phagocytosis, inflammation, scar formation, and therapeutic implications.
寻常痤疮中的巨噬细胞:介导吞噬作用、炎症、瘢痕形成及治疗意义。
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Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances.寻常痤疮:病理生理学、治疗及基于纳米技术的最新进展综述
Biochem Biophys Rep. 2023 Nov 23;36:101578. doi: 10.1016/j.bbrep.2023.101578. eCollection 2023 Dec.
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Antimicrobial peptide 2K4L disrupts the membrane of multidrug-resistant and protects mice against sepsis.抗菌肽2K4L破坏多重耐药菌的细胞膜并保护小鼠免受败血症侵害。
Front Microbiol. 2023 Oct 24;14:1258469. doi: 10.3389/fmicb.2023.1258469. eCollection 2023.
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Prevention of bacterial biofilm formation on orthodontic brackets by non-crosslinked chitosan coating.非交联壳聚糖涂层预防正畸托槽表面细菌生物膜的形成。
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Post-Inflammatory Hyperpigmentation in Dark Skin: Molecular Mechanism and Skincare Implications.深色皮肤的炎症后色素沉着:分子机制及皮肤护理意义
Clin Cosmet Investig Dermatol. 2022 Nov 25;15:2555-2565. doi: 10.2147/CCID.S385162. eCollection 2022.
8
Tryptophan, more than just an interfacial amino acid in the membrane activity of cationic cell-penetrating and antimicrobial peptides.色氨酸不仅仅是阳离子细胞穿透肽和抗菌肽在膜活性中的界面氨基酸。
Q Rev Biophys. 2022 Aug 18;55:e10. doi: 10.1017/S0033583522000105.
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Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug-resistant infections.抗菌肽、传统抗生素及其在治疗耐药性感染中的协同作用。
Med Res Rev. 2022 Jul;42(4):1377-1422. doi: 10.1002/med.21879. Epub 2022 Jan 4.
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JAMA. 2021 Nov 23;326(20):2055-2067. doi: 10.1001/jama.2021.17633.