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Synergistic anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and absolute stereochemistry of 7,8-dideoxygriseorhodin C
- Source :
- The Journal of Antibiotics
- Publication Year :
- 2019
-
Abstract
- 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−1. 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
- Subjects :
- Methicillin-Resistant Staphylococcus aureus
medicine.drug_class
Antibiotics
Enterococcus faecium
Microbial Sensitivity Tests
010402 general chemistry
medicine.disease_cause
Gram-Positive Bacteria
01 natural sciences
Streptomyces
Article
Microbiology
Antibiotic resistance
Drug Discovery
medicine
Spiro Compounds
Drug discovery and development
Oxacillin
Pharmacology
biology
010405 organic chemistry
Chemistry
Small molecules
Drug Synergism
biochemical phenomena, metabolism, and nutrition
Antimicrobial
biology.organism_classification
Methicillin-resistant Staphylococcus aureus
0104 chemical sciences
Anti-Bacterial Agents
Staphylococcus aureus
Bacteria
Naphthoquinones
Subjects
Details
- ISSN :
- 18811469
- Volume :
- 73
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The Journal of antibiotics
- Accession number :
- edsair.doi.dedup.....17771262559d59316778f591a7fd2550