Mycobacterium tuberculosisBeijing Genotype Resistance to Transient Rifampin Exposure

Alice L Den Hertog,Richard M Anthony,Sandra Menting,Dick Van Soolingen

doi:10.3201/eid2011.130560

Abstract

<i>Mycobacterium tuberculosis</i>Beijing Genotype Resistance to Transient Rifampin Exposure

Highlights

To the Editor: We read with interest the discussion between de Steenwinkel et al and Werngren [1] regarding the high mutation frequencies de Steenwinkel et al reported for some Mycobacterium tuberculosis strains [2]
We previously estimated the mutation rate of 1 of the strains tested at ≈1 × 10–7 [3], which is within the range typically reported for acquisition of rifampin resistance by strains from Beijing and other lineages of M. tuberculosis [4,5]
We propose an alternative interpretation of these findings on the basis of new experimental data (Figure). These data show that some M. tuberculosis strains persist longer than others after transient exposure to low concentrations of rifampin, which could create a wider window for the generation and selection of resistant mutants

Summary

Introduction

To the Editor: We read with interest the discussion between de Steenwinkel et al and Werngren [1] regarding the high mutation frequencies de Steenwinkel et al reported for some Mycobacterium tuberculosis strains [2]. Several explanations were proposed for the detection of a high frequency of mutants on rifampin exposure, mainly related to methods or experimental variation [1]. These data show that some M. tuberculosis strains persist longer than others after transient exposure to low concentrations of rifampin, which could create a wider window for the (possibly stimulated) generation and selection of resistant mutants.

Results

Conclusion