title: Mutations in rpoB gene and rifabutin susceptibility of multidrug-resistant Mycobacterium tuberculosis strains isolated in Australia.
abstract: Control of tuberculosis, the single largest killer among the infectious diseases, has been threatened by the emergence of multidrug-resistant Mycobacterium tuberculosis (MDRTB) infection due to the limited treatment options. Rifampicin (RIF) resistance is considered as a marker for MDRTB. The aim of this study was the detection of rpoB gene mutations and rifabutin resistance in MDRTB strains recently isolated in Australia by a line probe assay (INNO-LiPA Rif. TB, Innogenetics). Rifabutin and RIF susceptibility of 20 MDRTB and 16 RIF-sensitive M. tuberculosis complex clinical isolates were studied. The overall concordance of the line probe assay (LiPA) with phenotypic RIF susceptibility test was 96%. Seven distinct nucleotide substitutions were identified in 21 of 22 RIF-resistant isolates of diverse geographical origins, but in none of the RIF-sensitive strains. The majority (71%) of mutations occurred in the 526-533 codons and were associated with resistance to rifabutin and RIF. Of the RIF-resistant MDRTB strains, 18% appeared to be rifabutin-sensitive and produced delta S2 and delta S3 INNO-LiPA patterns. We conclude that amino acid substitutions at Asp516 and Ser522 in the rpoB gene in RIF-resistant M. tuberculosis predict rifabutin susceptibility for MDRTB. Use of the LiPA for RIF and rifabutin resistance may facilitate the rapid response required to limit the extent and severity of MDRTB transmission and infection.
authors.affiliation: Centre for Infectious Diseases, Westmead Hospital, New South Wales, Australia. vitalis@cidm.wsahs.nsw.gov.au
authors.forename: V
authors.initials: V
authors.lastname: Sintchenko
authors.forename: W K
authors.initials: WK
authors.lastname: Chew
authors.forename: P J
authors.initials: PJ
authors.lastname: Jelfs
authors.forename: G L
authors.initials: GL
authors.lastname: Gilbert
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001315:Australia; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D017354:Point Mutation; D017828:Rifabutin / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit