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.
Highlights
The rapid rise of methicillin-resistant Staphylococcus aureus (MRSA) infections worldwide has defined an urgent need for new antibiotics
We observed that napyradiomycins from the marine strain CNQ-525 could show activities against a test strain of MRSA and vancomycin-resistant Enterococcus (VRE) [17]
We investigated in detail the antibiotic properties of napyradiomycins against a panel of clinically relevant MRSA strains
Summary
The rapid rise of methicillin-resistant Staphylococcus aureus (MRSA) infections worldwide has defined an urgent need for new antibiotics. Fenical and colleagues recently isolated the marine-derived actinomycete strain, CNQ-525, that was found to be a member of the MAR 4 group of Streptomyces related bacteria [15,16,17,18]. This strain was found to produce chlorine-containing meroterpenoids of the napyradiomycin class [17,18]. Our data illustrate that select napyradiomycins, while cytotoxic, are potent anti-MRSA antibiotics with rapid in vitro time kill kinetics
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