Acquisition of rifabutin resistance by a rifampicin resistant mutant of Mycobacterium tuberculosis involves an unusual spectrum of mutations and elevated frequency

• Published in: Annals of clinical microbiology and antimicrobials 2005-06, Vol.4 (1), p.9-9, Article 9
• Main Authors: Anthony, Richard M, Schuitema, Anja R J, Bergval, Indra L, Brown, Tim J, Oskam, Linda, Klatser, Paul R
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Codon; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Rifabutin - pharmacology; Rifampin - pharmacology
• ISSN: 1476-0711; 1476-0711
• DOI: 10.1186/1476-0711-4-9

Mutations in a small region of the rpoB gene are responsible for most rifamycin resistance in Mycobacterium tuberculosis. In this study we have sequentially generated resistant strains to first rifampicin and then rifabutin. Portions of the rpoB gene were sequenced from 131 randomly selected mutants. Second round selection resulted in a changed frequency of specific mutations. Mycobacterium tuberculosis (strain Mtb72) rifamycin resistant mutants were selected in vitro with either rifampicin or rifabutin. One mutant R190 (rpoB S522L) selected with rifampicin had a rifampicin MIC of 32 microg/ml but remained sensitive to rifabutin (MIC10 times the frequency by the S522L mutant than the parent strain. First round selection of mutation S522L with rifampicin increased the frequency and changed the spectrum of mutations identified after selection with rifabutin.