Abstract |
The alarming rise of hospital- and community-associated methicillin-resistant Staphylococcus aureus (HA- and CA-MRSA) infections has prompted a desperate search for novel antibiotics. We discovered the streptogramin etamycin produced by an actinomycete species isolated from the coast of Fiji, the first time this antibiotic has been identified from a marine microbe. Etamycin was extracted and purified from this strain (CNS-575) and identified as a three-rotamer species by 2D NMR spectroscopy. Etamycin demonstrated potent activity against HA- and CA-MRSA in microbroth dilution assays, with minimum inhibitory concentrations (MIC) as low as 1-2 mg l(-1) against HA- and CA-MRSA strains. Furthermore, etamycin was also active against other Gram-positive and several Gram-negative pathogens and was found to be non-cytotoxic at concentrations more than 20-fold above MIC. Etamycin displayed favorable time-kill kinetics compared with the first-line MRSA antibiotic, vancomycin, and also conferred significant protection from mortality in a murine model of systemic lethal MRSA infection. These data emphasize the utility of the marine environment as a relatively untapped source of antibiotics against major drug-resistant human pathogens. These studies will also guide future isolation and preclinical development of depsipeptide anti-MRSA compounds from marine-derived actinomycetes.
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Authors | Nina M Haste, Varahenage R Perera, Katherine N Maloney, Dan N Tran, Paul Jensen, William Fenical, Victor Nizet, Mary E Hensler |
Journal | The Journal of antibiotics
(J Antibiot (Tokyo))
Vol. 63
Issue 5
Pg. 219-24
(May 2010)
ISSN: 1881-1469 [Electronic] England |
PMID | 20339399
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Anti-Bacterial Agents
- Macrolides
- etamycin
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Topics |
- Actinobacteria
(metabolism)
- Animals
- Anti-Bacterial Agents
(chemistry, isolation & purification, pharmacology, therapeutic use)
- Female
- Macrolides
(chemistry, isolation & purification, pharmacology, therapeutic use)
- Magnetic Resonance Spectroscopy
- Methicillin-Resistant Staphylococcus aureus
(drug effects)
- Mice
- Microbial Sensitivity Tests
- Staphylococcal Infections
(drug therapy)
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