Marine-derived new peptaibols with antibacterial activities by targeting bacterial membrane phospholipids

IF 14.7 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B Pub Date : 2025-05-01 DOI:10.1016/j.apsb.2025.02.036

Shang Chen , Dong Liu , Liyang Wang , Aili Fan , Mengyue Wu , Ning Xu , Kui Zhu , Wenhan Lin

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引用次数: 0

Abstract

Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

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以细菌膜磷脂为靶点的新型抗菌肽

抗生素耐药性的蔓延速度比用于临床治疗的新抗生素更快。迫切需要发现对抗多药耐药（MDR）细菌的潜在化合物。海洋真菌为挖掘具有化学多样性的类抗生素分子提供了一条有前途的途径。为了发现结构新颖的抗生素代谢物，我们对海洋真菌基因组文库进行了筛选，发现含有18个模块的非核糖体肽合成酶（NRPS）簇的真菌Stephanonectria keithii LZD-10-1合成了一个新的肽亚家族，可以有效地根除耐多药耐药性病原体。培养真菌的靶向分离得到了6种新的肽，它们通过靶向细菌膜磷脂，特别是磷脂酰甘油（PG）来杀死耐多药细菌，从而导致细菌膜功能障碍。此外，我们还观察了它们对耐甲氧西林金黄色葡萄球菌（MRSA）的治疗效果。这项研究强调了采用基因组引导方法鉴定未开发的海洋真菌作为具有独特支架的新型抗生素候选物的潜在来源的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Pharmaceutica Sinica. B Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

22.40

自引率

5.50%

发文量

1051

审稿时长

19 weeks

期刊介绍： The Journal of the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association oversees the peer review process for Acta Pharmaceutica Sinica. B (APSB). Published monthly in English, APSB is dedicated to disseminating significant original research articles, rapid communications, and high-quality reviews that highlight recent advances across various pharmaceutical sciences domains. These encompass pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis, and pharmacokinetics. A part of the Acta Pharmaceutica Sinica series, established in 1953 and indexed in prominent databases like Chemical Abstracts, Index Medicus, SciFinder Scholar, Biological Abstracts, International Pharmaceutical Abstracts, Cambridge Scientific Abstracts, and Current Bibliography on Science and Technology, APSB is sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association. Its production and hosting are facilitated by Elsevier B.V. This collaborative effort ensures APSB's commitment to delivering valuable contributions to the pharmaceutical sciences community.