菊粉肽对新出现的机会性病原体脓肿分枝杆菌具有良好的抗菌效果。

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2024-01-29 DOI:10.1186/s12929-024-01007-8
Magali Casanova, Marc Maresca, Isabelle Poncin, Vanessa Point, Hamza Olleik, Céline Boidin-Wichlacz, Aurélie Tasiemski, Kamel Mabrouk, Jean-François Cavalier, Stéphane Canaan
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引用次数: 0

摘要

背景:脓肿分枝杆菌是一种快速生长的非结核分枝杆菌,是一种新出现的机会性病原体,可导致囊性纤维化(CF)等呼吸系统疾病患者的慢性支气管肺部感染。由于脓肿分枝杆菌对多种抗生素具有固有的多重抗药性,大多数治疗脓肿分枝杆菌肺部感染的方法效果不佳。在这种情况下,抗菌肽(AMPs)对细菌菌株具有活性,且不易产生抗药性,是传统抗生素的良好替代品。在此,我们评估了三种拥有两个或四个半胱氨酸、参与一个(Ar-1、Ar-2)或两个二硫键(Ar-3)的异构体 arenicin 对脓肿霉菌体外生长的影响:方法:通过用α-氨基丁酸(Abu)残基取代半胱氨酸,构建了相应的无二硫键 AMP。我们评估了这八种鸟嘌呤衍生物对脓肿霉菌株的抗菌活性、对人类细胞系的细胞毒性以及对人类红细胞的溶血活性。通过膜渗透试验、电子显微镜、表面压力测量的脂质插入试验以及抗药性诱导试验,进一步研究了 Ar-1 肽的作用机制:结果:我们的研究结果表明,Ar-1 是最安全的多肽,对人体细胞无毒性,无溶血活性,对脓肿霉菌的生长最有效。Ar-1 通过插入分枝杆菌脂质发挥作用,从而产生快速溶膜效应,杀死脓肿霉菌而不诱导抗药性:总之,本研究强调了 Ar-1 在治疗与脓肿霉菌有关的 CF 相关细菌感染方面,是传统抗生素的潜在新替代品。
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Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus.

Background: Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective. In this context, antimicrobial peptides (AMPs) active against bacterial strains and less prompt to cause resistance, represent a good alternative to conventional antibiotics. Herein, we evaluated the effect of three arenicin isoforms, possessing two or four Cysteines involved in one (Ar-1, Ar-2) or two disulfide bonds (Ar-3), on the in vitro growth of M. abscessus.

Methods: The respective disulfide-free AMPs, were built by replacing the Cysteines with alpha-amino-n-butyric acid (Abu) residue. We evaluated the efficiency of the eight arenicin derivatives through their antimicrobial activity against M. abscessus strains, their cytotoxicity towards human cell lines, and their hemolytic activity on human erythrocytes. The mechanism of action of the Ar-1 peptide was further investigated through membrane permeabilization assay, electron microscopy, lipid insertion assay via surface pressure measurement, and the induction of resistance assay.

Results: Our results demonstrated that Ar-1 was the safest peptide with no toxicity towards human cells and no hemolytic activity, and the most active against M. abscessus growth. Ar-1 acts by insertion into mycobacterial lipids, resulting in a rapid membranolytic effect that kills M. abscessus without induction of resistance.

Conclusion: Overall, the present study emphasized Ar-1 as a potential new alternative to conventional antibiotics in the treatment of CF-associated bacterial infection related to M. abscessus.

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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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