RIBOSYLATIVE INACTIVATION OF RIFAMPIN BY MYCOBACTERIUM-SMEGMATIS IS APRINCIPAL CONTRIBUTOR TO ITS LOW SUSCEPTIBILITY TO THIS ANTIBIOTIC

Mycobacterium smegmatis inactivates rifampin by ribosylating this anti biotic. The gene responsible for this ability was cloned and was shown to confer low-level resistance to this antibiotic (MIC increase, abou t 12-fold) in related organisms. A 600-bp subclone responsible for rib osylating activity and resistance carried an open reading frame of 429 bp. Targeted disruption of the gene in M. smegmatis resulted in mutan ts with much increased susceptibility to rifampin (MICs of 1.5 instead of 20 mu g/ml) as well as the loss of antibiotic-inactivating ability . Also, disruption of this gene led to a much lower frequency of occur rence of spontaneous high-level rifampin-resistant mutants.