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• Haste, N
• Farnaes, L
• Perera, V
• Fenical, W
• Nizet, V
• Hensler, M
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• Haste, N
• Farnaes, L
• Perera, V
• Fenical, W
• Nizet, V
• Hensler, M
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• Haste, N
• Farnaes, L
• Perera, V
• Fenical, W
• Nizet, V
• Hensler, M

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Mar. Drugs 2011, 9(4), 680-689; doi:10.3390/md9040680

Article

Bactericidal Kinetics of Marine-Derived Napyradiomycins against Contemporary Methicillin-Resistant Staphylococcus aureus

Nina M. Haste ^1,2 , Lauge Farnaes ^2,3 , Varahenage R. Perera ³ , William Fenical ^1,2 , Victor Nizet ^1,3  and Mary E. Hensler ^3,*

¹ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA ² Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA ³ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA

* Author to whom correspondence should be addressed.

Received: 16 December 2010; in revised form: 15 February 2011 / Accepted: 13 April 2011 / Published: 21 April 2011

(This article belongs to the Special Issue Marine Antibiotics)

Download PDF Full-Text [262 KB, uploaded 21 April 2011 14:59 CEST]

Abstract: There is an urgent need for new antibiotics to treat hospital- and community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous work has indicated that both terrestrial and marine-derived members of the napyradiomycin class possess potential anti-staphylococcal activities. These compounds are unique meroterpenoids with unusual levels of halogenation. In this paper we report the evaluation of two previously described napyradiomycin derivatives, A80915A (1) and A80915B (2) produced by the marine-derived actinomycete, Streptomyces sp. strain CNQ-525, for their specific activities against contemporary and clinically relevant MRSA. Reported are studies of the in vitro kinetics of these chemical scaffolds in time-kill MRSA assays. Both napyradiomycin derivatives demonstrate potent and rapid bactericidal activity against contemporary MRSA strains. These data may help guide future development and design of analogs of the napyradiomycins that could potentially serve as useful anti-MRSA therapeutics.

Keywords: napyradiomycin; antibiotic; antibacterial; time-kill; methicillin-resistant Staphylococcus aureus (MRSA)

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