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Against the virginiamycin group of antibiotics, to which etamycin belongs, two mechanisms of resistance are known - enzymic inactivation and target site modification. No etamycin inactivating activity was detected either extracellularly or in cell extracts of S. griseoviridis. Since target site modification in MLS-type antibiotics (which include etamycin and erythromycin) involves 23S rRNA modification, an internal fragment of the previously characterized ermE gene which confers erythromycin resistance on the erythromycin producer, was used to probe for hybridizing DNA fragments in an S. griseoviridis genomic library. A lambda clone containing 17 kb of S. griseoviridis DNA was thereby detected. The fragment was isolated and was subcloned into the Streptomyces - Escherichia coli shuttle vector, pHJL400. When the recombinant plasmid was introduced into an etamycin-sensitive host, Streptomyces griseofuscus, the resulting transformants were all etamycin resistant. The etamycin resistance gene has been localized to an 8-kb SstI subfragment of the original clone. Characterization of the gene and the resistance mechanism it confers is in progress.
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