Novel Insights into the Nobilamide Family from a Deep-Sea Bacillus: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria.

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL Marine Drugs Pub Date : 2025-01-14 DOI:10.3390/md23010041

Vincenza Casella, Gerardo Della Sala, Silvia Scarpato, Carmine Buonocore, Costanza Ragozzino, Pietro Tedesco, Daniela Coppola, Giovanni Andrea Vitale, Donatella de Pascale, Fortunato Palma Esposito

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Abstract

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase.

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深海芽孢杆菌Nobilamide家族的新发现：化学多样性，生物合成和对多重耐药细菌的抗菌活性。

随着人们对抗菌素耐药性的日益关注，鉴定针对多重耐药细菌的新先导化合物至关重要。本研究采用快速小型化筛选的方法，同时培养和评价了约300株海洋菌株的生物表面活性剂和抗菌活性，最终筛选出深海耐盐芽孢杆菌BCP32。串联质谱分子网络和生物测定引导分离的整合揭示了该菌株是一个多产的表面素和诺比酰胺工厂。特别是，在细菌外代谢组中鉴定出84个nobilamide同源物，其中71个是新的代谢物。其中，主要分离到4个化合物，包括已知的TL-119和nobilamide I，以及两个新的nobilamide T1和S1。TL-119和nobilamide S1对多种多重耐药葡萄球菌菌株和其他革兰氏阳性病原体（包括食源性单核细胞增生李斯特菌）具有有效的抗生素活性。最后，对耐盐芽孢杆菌BCP32基因组的计算机分析显示，诺bilamide的生物合成是由一种以前未知的七分子非核糖体肽合成酶指导的。

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

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.