Affiliation:
1. Department of Infection, Guy's, King's and St. Thomas' School of Medicine, St. Thomas' Hospital, London SE1 7EH, United Kingdom
Abstract
ABSTRACT
Rifampin is the most potent drug used in the treatment of disease due to
Mycobacterium kansasii
. A 69-bp fragment of
rpoB
, the gene that encodes the β subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of
M. kansasii
. This sequence showed 87% homology with the
Mycobacterium tuberculosis
gene, with an identical deduced amino acid sequence. In contrast, missense mutations were detected in the same fragment amplified from five rifampin-resistant isolates. A rifampin-resistant strain generated in vitro also harbored an
rpoB
gene missense mutation that was not present in the parent isolate. All mutations detected (in codons 513, 526, and 531) have previously been described in rifampin-resistant
M. tuberculosis
isolates. Rifampin MICs determined 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 five rifampin-resistant isolates were also resistant to rifabutin. We have thus shown a strong association between
rpoB
gene missense mutations and rifampin resistance in
M. kansasii
. Although our results are derived from a small 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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