Affiliation:
1. Institut fuer Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Regensburg,1 and
2. Forschungszentrum Borstel, National Reference Center for Mycobacteria, Borstel,2 Germany
Abstract
ABSTRACT
The prevalence of recently described mutation V176F, located in the beginning of the
rpoB
gene and associated with rifampin resistance and the wild-type cluster I sequence, was determined by analyzing the distribution of
rpoB
mutations among 80 rifampin (RIF)-resistant
Mycobacterium tuberculosis
strains isolated in Germany during 1997. The most frequent
rpoB
mutations were changes in codon 456 (52 isolates, 65%), followed by changes in codon 441 (13 isolates, 16%) and codon 451 (11 isolates, 14%). The V176F mutation was detected in one isolate of the study population and in 5 of 18 RIF-resistant strains with no cluster I mutation from six previously published studies. In three isolates, a mixture of resistant and susceptible subpopulations (heteroresistance) prohibited the detection of
rpoB
mutations in the initial analysis; however, in these isolates, cluster I mutations could be verified after a passage on RIF-containing medium. IS
6110
DNA fingerprinting of 76 strains revealed eight clusters comprising 27 strains with identical restriction fragment length polymorphism patterns that mainly also show identical
rpoB
mutations and identical or similar drug resistance patterns. In conclusion, our results indicate that the V176F mutation should be included in molecular tests for prediction of RIF resistance in
M. tuberculosis
. We further demonstrated that heteroresistance caused by a mixture of mycobacterial subpopulations with different susceptibilities to RIF may influence the sensitivity of molecular tests for detection of resistance.
Publisher
American Society for Microbiology
Cited by
194 articles.
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