Rifampin resistance in Mycobacterium kansasii is associated with rpoB mutations

Rifampin is the most potent drug used in the treatment of disease due to My cobacterium kansasii. A 69-bp fragment of rpoB, the gene that encodes the b eta subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of M. kansasii. Th is sequence showed 87% homology with the Mycobacterium tuberculosis gene, w ith an identical deduced amino acid sequence. In contrast, missense mutatio ns were detected in the same fragment amplified from five rifampin-resistan t isolates. A rifampin-resistant strain generated in vitro also harbored an rpoB gene missense mutation that was not present in the parent isolate. Al l mutations detected (in codons 513, 526, and 531) have previously been des cribed in rifampin-resistant M. tuberculosis isolates. Rifampin MICs determ ined by E-test were < 1 mg/liter for all rifampin-susceptible isolates and > 256 mg/liter for all rifampin-resistant ones. In addition, four of the fi ve rifampin-resistant isolates were also resistant to rifabutin. We have th us shown a strong association between rpoB gene missense mutations and rifa mpin resistance in M. kansasii. Although our results are derived from a sma ll number of isolates and confirmation with larger numbers would be useful, they strongly suggest that mutations within rpoB form the molecular basis of rifampin resistance in this species.