Arcopilins: A New Family of Staphylococcus aureus Biofilm Disruptors from the Soil Fungus Arcopilus navicularis

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Název: Arcopilins: A New Family of Staphylococcus aureus Biofilm Disruptors from the Soil Fungus Arcopilus navicularis
Autoři: Esteban Charria-Girón, Haoxuan Zeng, Tatiana E. Gorelik, Alexandra Pahl, Khai-Nghi Truong, Hedda Schrey, Frank Surup, Yasmina Marin-Felix
Zdroj: J Med Chem
Informace o vydavateli: American Chemical Society (ACS), 2024.
Rok vydání: 2024
Témata: Staphylococcus aureus, Pyridones, Biofilms, Pyridones/chemistry [MeSH], Staphylococcus aureus/drug effects [MeSH], Pyridones/chemical synthesis [MeSH], Pyridones/pharmacology [MeSH], Pyrrolidinones/chemistry [MeSH], Pyrrolidinones/pharmacology [MeSH], Soil Microbiology [MeSH], Article, Biofilms/drug effects [MeSH], Anti-Bacterial Agents/chemistry [MeSH], Anti-Bacterial Agents/pharmacology [MeSH], Pyrrolidinones/metabolism [MeSH], Microbial Sensitivity Tests [MeSH], Microbial Sensitivity Tests, Soil Microbiology, Pyrrolidinones, Anti-Bacterial Agents
Popis: Biofilms represent a key challenge in the treatment of microbial infections; for instance, Staphylococcus aureus causes chronic or fatal infections by forming biofilms on medical devices. Herein, the fungus Arcopilus navicularis was found to produce a novel family of PKS-NRPS metabolites that are able to disrupt preformed biofilms of S. aureus. Arcopilins A-F (1-6), tetramic acids, and arcopilin G (7), a 2-pyridone, were elucidated using HR-ESI-MS and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Their absolute configuration was established by the synthesis of MPTA-esters for 2, analysis of 1H-1H coupling constants, and ROESY correlations, along with comparison with the crystal structure of 7. Arcopilin A (1) not only effectively disrupts preformed biofilms of S. aureus but also potentiates the activity of gentamicin and vancomycin up to 115- and 31-fold times, respectively. Our findings demonstrate the potential application of arcopilins for the conjugated treatment of infections caused by S. aureus with antibiotics unable to disrupt preformed biofilms.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1520-4804
0022-2623
DOI: 10.1021/acs.jmedchem.4c00585
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39141525
https://repository.publisso.de/resource/frl:6486244
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (http://creativecommons.org/licenses/by/4.0/).
Přístupové číslo: edsair.doi.dedup.....bb8bda2f8e95873f630583ae4c3e8463
Databáze: OpenAIRE
Popis
Abstrakt:Biofilms represent a key challenge in the treatment of microbial infections; for instance, Staphylococcus aureus causes chronic or fatal infections by forming biofilms on medical devices. Herein, the fungus Arcopilus navicularis was found to produce a novel family of PKS-NRPS metabolites that are able to disrupt preformed biofilms of S. aureus. Arcopilins A-F (1-6), tetramic acids, and arcopilin G (7), a 2-pyridone, were elucidated using HR-ESI-MS and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Their absolute configuration was established by the synthesis of MPTA-esters for 2, analysis of 1H-1H coupling constants, and ROESY correlations, along with comparison with the crystal structure of 7. Arcopilin A (1) not only effectively disrupts preformed biofilms of S. aureus but also potentiates the activity of gentamicin and vancomycin up to 115- and 31-fold times, respectively. Our findings demonstrate the potential application of arcopilins for the conjugated treatment of infections caused by S. aureus with antibiotics unable to disrupt preformed biofilms.
ISSN:15204804
00222623
DOI:10.1021/acs.jmedchem.4c00585