Frequency of rpoB Mutations Inside and Outside the Cluster I Region in Rifampin-Resistant Clinical Mycobacterium tuberculosis Isolates

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. IS6110 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.

Mutations in rpoB and katG genes in Mycobacterium isolates from the Southeast of Mexico

“…On the other hand, no mutations were observed in the rpoB gene. A similar result was previously reported in other Rif r isolates, with the mutations being located outside the RRDR (Heep et al 2000(Heep et al , 2001. Currently, we are working on identifying mutations in the complete rpoB gene from isolate 497.…”

Evaluation of Genotype® MTBDRplus Assay for Rapid Detection of Resistance to Isoniazid and Rifampin in Mycobacterium tuberculosis Isolates Collected in Tunisia

“…With respect to culture isolates, the sensitivities of the MTBDR assay for the detection of RIF resistance were recently reported to be in the range of 95% to 99% [9][10][11][12]. Both the rarity of RMP-resistance-associated mutations in codons other than the rpoB 81-bp hot spot region and the rarity of silent mutations in the hot spot region are responsible for the high rate of detection of RMP resistance by investigation of this region [12][13][14]. However, in our study sensitivity of the MTBDRplus assay measured for resistance to RIF was lower than those reported.…”

Detección de mutaciones asociadas a cepas multidrogo resistente de Mycobacterium tuberculosis en Chile

“…En 3 cepas resistentes a RIF no se detectaron mutaciones en la región del gen rpoβ que se estudió. Este resultado indica que la resistencia a RIF en estas cepas, podría estar relacionado con mutaciones en otra región del gen rpoβ o que otro mecanismo diferente es responsable de esta resistencia 30 .…”