Rifampicin acts by binding to the β-subunit of the RNA polymerase (RNAP, encoded by the rpoB gene), preventing the extension of the RNA (Fig. ). The most common resistance-conferring mutation is rpoB S450L, however a wide range of mutations have been observed clinically . The majority of these are found in amino acids 428 to 452 which pack against the drug (usually known as the "rifampicin resistance determining region" or RRDR), enabling the development of nucleic acid amplification tests, such as the Cepheid GeneXpert MTB/RIF system which is endorsed by the WHO for diagnosis of MDR-TB . Not all non-synonymous mutations in the RRDR, however, confer resistance, for example rpoB L443F . Nor does resistance arise purely within the RRDR: rpoB I491F and V170F are proximal to S450L and the former was suspected to be behind an outbreak of MDR-TB in Eswatini since it is not detected by GeneXpert .