Mutations in rpoB gene and rifabutin susceptibility of multidrug-resistantMycobacterium tuberculosis strains isolated in Australia

Control of tuberculosis, the single largest killer among the infectious dis eases, has been threatened by the emergence of multidrug-resistant Mycobact erium 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 resistan ce in MDRTB strains recently isolated in Australia by a line probe assay (I NNO-LiPA Rif.TB, Innogenetics). Rifabutin and RIF susceptibility of 20 MDRT B and 16 RIF-sensitive M. tuberculosis complex clinical isolates were studi ed. The overall concordance of the line probe assay (LiPA) with phenotypic RIF susceptibility test was 96%. Seven distinct nucleotide substitutions we re identified in 21 of 22 RIF-resistant isolates of diverse geographical or igins, but in none of the RIF-sensitive strains. The majority (71%) of muta tions occured in the 526-533 codons and were associated with resistance to rifabutin and RIF. Of the RIF-resistant MDRTB strains, 18% appeared to be r ifabutin-sensitive and produced Delta S2 and Delta S3 INNO-LiPA patterns. W e conclude that amino acid substitutions at Asp(516) and Ser(522) in the rp oB gene in RIF-resistant M. tuberculosis predict rifabutin susceptibility f or MDRTB. Use of the LiPA for RIF and rifabutin resistance may facilitate t he rapid response required to limit the extent and severity of MDRTB transm ission and infection.