title: Association of rpoB mutations with rifampicin resistance in Mycobacterium avium.
abstract: The susceptibility of clinical isolates of Mycobacterium avium to rifampicin (RIF) was examined. All 32 clinical isolates tested, including 18 from Japan, 13 from Poland and 1 from Thailand, were resistant to RIF (minimum inhibitory concentrations (MICs) > or =32 microg/mL for 17 isolates and 2-16 microg/mL for 15 isolates), whereas the type strain of M. avium ATCC 25291 was susceptible to RIF (MIC < or = 0.03 microg/mL). Mutations in nucleotides 1276-1356 of the rpoB gene, termed the 81 bp core region, are associated with RIF resistance in Mycobacterium tuberculosis. No mutations were found in this region in any of the M. avium clinical isolates tested. However, mutation of G-->A to give a Gly544-->Asp substitution was identified within the rpoB gene downstream of the 81 bp region in all clinical isolates. A RIF-resistant strain (ATCC 25291 Rif(r); MIC> or =32 microg/mL) obtained by culturing the type strain in RIF-containing broth possessed a mutation C-->T to give a His445-->Tyr substitution within the 81 bp region. When the rpoB gene of the ATCC 25291 Rif(r) strain and of a clinical isolate were inserted into Mycobacterium smegmatis, organisms with the ATCC 25291 Rif(r) sequence, but not those with the clinical isolate sequence, showed resistance to RIF. These results suggest that mutations of the 81 bp region of rpoB, as well as factors other than rpoB mutation, confer RIF resistance in M. avium.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Saiko
authors.initials: S
authors.lastname: Obata
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zwolska
authors.forename: Emiko
authors.initials: E
authors.lastname: Toyota
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kudo
authors.forename: Akio
authors.initials: A
authors.lastname: Nakamura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sawai
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Kuratsuji
authors.forename: Teruo
authors.initials: T
authors.lastname: Kirikae
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009162:Mycobacterium avium / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology*; D014169:Transformation, Bacterial
chemical_list: D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin