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Synergistic anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and absolute stereochemistry of 7,8-dideoxygriseorhodin C
Journal article   Open access   Peer reviewed

Synergistic anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and absolute stereochemistry of 7,8-dideoxygriseorhodin C

Bailey W Miller, Joshua P Torres, Jortan O Tun, Malem S Flores, Imelda Forteza, Gary Rosenberg, Margo G Haygood, Eric W Schmidt and Gisela P Concepcion
Journal of antibiotics, v 73(5)
May 2020
DOI: https://doi.org/10.1038/s41429-019-0275-8
PMID: 31992865
url
https://doi.org/10.1038/s41429-019-0275-8View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - isolation & purification Anti-Bacterial Agents - pharmacology Drug Synergism Enterococcus faecium - drug effects Gram-Positive Bacteria - drug effects Methicillin-Resistant Staphylococcus aureus - drug effects Microbial Sensitivity Tests Naphthoquinones - administration & dosage Naphthoquinones - chemistry Naphthoquinones - isolation & purification Naphthoquinones - pharmacology Oxacillin - administration & dosage Oxacillin - pharmacology Spiro Compounds - administration & dosage Spiro Compounds - chemistry Spiro Compounds - isolation & purification Spiro Compounds - pharmacology Streptomyces - metabolism
The emergence of antibiotic resistance necessitates not only the identification of new compounds with antimicrobial properties, but also new strategies and combination therapies to circumvent this growing problem. Here, we report synergistic activity against methicillin-resistant Staphylococcus aureus (MRSA) of the β-lactam antibiotic oxacillin combined with 7,8-dideoxygriseorhodin C in vitro. Ongoing efforts to identify antibiotics from marine mollusk-associated bacteria resulted in the isolation of 7,8-dideoxygriseorhodin C from a Streptomyces sp. strain cultivated from a marine gastropod tissue homogenate. Despite the long history of 7,8-dideoxygriseorhodin C in the literature, the absolute configuration has never been previously reported. A comparison of measured and calculated ECD spectra resolved the configuration of the spiroketal carbon C6, and 2D ROESY NMR spectroscopy established the absolute configuration as 6s,6aS. The compound is selective against Gram-positive bacteria including MRSA and Enterococcus faecium with an MIC range of 0.125-0.5 μg ml . Moreover, the compound synergizes with oxacillin against MRSA as observed in the antimicrobial microdilution and time-kill assays. Simultaneous treatment of the compound with oxacillin resulted in an approximately tenfold decrease in MIC with a combination index of <0.5, indicating synergistic anti-MRSA activity.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biotechnology & Applied Microbiology
Immunology
Microbiology
Pharmacology & Pharmacy
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