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

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

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 a...

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Main Authors: Vincenza Casella, Gerardo Della Sala, Silvia Scarpato, Carmine Buonocore, Costanza Ragozzino, Pietro Tedesco, Daniela Coppola, Giovanni Andrea Vitale, Donatella de Pascale, Fortunato Palma Esposito
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Marine Drugs
Subjects:
<i>Bacillus</i>
antimicrobials
nobilamides
surfactins
MDR <i>Staphyloccus aureus</i>
<i>Listeria monocytogenes</i>
Online Access:https://www.mdpi.com/1660-3397/23/1/41
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Summary: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 <i>Bacillus halotolerans</i> 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 <i>Staphylococcus</i> strains and other Gram-positive pathogens, including the foodborne pathogen <i>Listeria monocytogenes</i>. Finally, in silico analysis of <i>Bacillus halotolerans</i> BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase.
ISSN:1660-3397

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