The Molecular Mechanism and WHO-endorsed Diagnosis of Rifampicin Resistance in Mycobacterium tuberculosis

Rifampicin is one of first-line drugs used in the treatment of tuberculosis (TB). Increasing rifampicin resistance hampers effective TB treatment. Resistance to rifampicin is commonly caused by mutation in the rpoB gene encoding the β–subunit of RNA polymerase. Mutations of 81-bp rifampicin resistance-determining region (RRDR) of the rpoB gene associate with most of rifampicin resistance in clinical strains. However, mutations outside RRDR and efflux pumps have been reported to be involved in rifampicin resistance. Rapid test for rifampicin resistance is important for improving patient care and decreasing TB transmission. World health organization (WHO) has endorsed rapid phenotypic tests, microscopic observation of drug susceptibility (MODS), nitrate reductase assay (NRA) and colorimetric redox indicator (CRI), and molecular tests, INNO-LiPA Rif. TB, Xpert® MTB/RIF test, GenoType® MTBDR assay and GenoType® MTBDRplus assay, for rifampicin resistance and recommended the use of rapid tests in high risk multidrug-resistant TB (MDR-TB) settings. This review article focuses on the various site mutation in rpoB associated with mycobacterial rifampicin resistance and summarizes the performance of these WHO-endorsed rapid tests for rifampicin resistance.