Journal
JOURNAL OF ANTIBIOTICS
Volume 62, Issue 2, Pages 55-61Publisher
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2008.8
Keywords
antisense; natural products; RNA synthesis inhibitors; rpsD
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Protein synthesis inhibition is a highly successful target for developing clinically effective and safe antibiotics. There are several targets within the ribosomal machinery, and small ribosomal protein S4 (RPSD) is one of the newer targets. Screening of microbial extracts using antisense-sensitized rpsD Staphylococcus aureus strain led to isolation of okilactomycin and four new congeners from Streptomyces scabrisporus. The major compound, okilactomycin, was the most active, with a minimum detection concentration of 3-12 mu g ml(-1) against antisense assay, and showed an MIC of 4-16 mu g ml(-1) against Gram-positive bacteria, including S. aureus. The congeners were significantly less active in all assays, and all compounds showed a slight preferential inhibition of RNA synthesis over DNA and protein synthesis. Antisense technology, due to increased sensitivity, continues to yield new, even though weakly active, antibiotics.
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