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
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Online Access:https://www.mdpi.com/1660-3397/23/1/41
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author Vincenza Casella
Gerardo Della Sala
Silvia Scarpato
Carmine Buonocore
Costanza Ragozzino
Pietro Tedesco
Daniela Coppola
Giovanni Andrea Vitale
Donatella de Pascale
Fortunato Palma Esposito
author_facet Vincenza Casella
Gerardo Della Sala
Silvia Scarpato
Carmine Buonocore
Costanza Ragozzino
Pietro Tedesco
Daniela Coppola
Giovanni Andrea Vitale
Donatella de Pascale
Fortunato Palma Esposito
author_sort Vincenza Casella
collection DOAJ
description 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.
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spelling doaj-art-95b925c4732e476e9cfb6da4ebdae13e2025-01-24T13:39:36ZengMDPI AGMarine Drugs1660-33972025-01-012314110.3390/md23010041Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant BacteriaVincenza Casella0Gerardo Della Sala1Silvia Scarpato2Carmine Buonocore3Costanza Ragozzino4Pietro Tedesco5Daniela Coppola6Giovanni Andrea Vitale7Donatella de Pascale8Fortunato Palma Esposito9Department of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyDepartment of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Via A.F. Acton, 55, 80133 Naples, ItalyWith 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.https://www.mdpi.com/1660-3397/23/1/41<i>Bacillus</i>antimicrobialsnobilamidessurfactinsMDR <i>Staphyloccus aureus</i><i>Listeria monocytogenes</i>
spellingShingle Vincenza Casella
Gerardo Della Sala
Silvia Scarpato
Carmine Buonocore
Costanza Ragozzino
Pietro Tedesco
Daniela Coppola
Giovanni Andrea Vitale
Donatella de Pascale
Fortunato Palma Esposito
Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
Marine Drugs
<i>Bacillus</i>
antimicrobials
nobilamides
surfactins
MDR <i>Staphyloccus aureus</i>
<i>Listeria monocytogenes</i>
title Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
title_full Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
title_fullStr Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
title_full_unstemmed Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
title_short Novel Insights into the Nobilamide Family from a Deep-Sea <i>Bacillus</i>: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
title_sort novel insights into the nobilamide family from a deep sea i bacillus i chemical diversity biosynthesis and antimicrobial activity towards multidrug resistant bacteria
topic <i>Bacillus</i>
antimicrobials
nobilamides
surfactins
MDR <i>Staphyloccus aureus</i>
<i>Listeria monocytogenes</i>
url https://www.mdpi.com/1660-3397/23/1/41
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