SUMMARY: Resistance to the endogenous antibiotic was studied in three actinomycetes that produce inhibitors of RNA polymerase. The three producers, (rifamycin producer), (streptovaricin producer) and (streptolydigin producer), were each highly resistant to the antibiotic they produce (MIC >200 μg ml) and RNA synthesis was also resistant. However, cross-resistance to the other RNA polymerase inhibitors was not found. Resistance to these antibiotics was due to target site modification, since the RNA polymerase enzymes of the three producing organisms were highly resistant to the corresponding antibiotic, and no antibiotic-inactivating enzymes were detected. A mutant was isolated from which was sensitive to steptovaricin (its own product) and also showed an increased sensitivity to rifamycin and streptolydigin. This mutant had RNA polymerase which was extremely sensitive to the three antibiotics.


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