rpoB

The rpoB gene encodes the β subunit of bacterial RNA polymerase. It is the site of mutations that confer resistance to the rifamycin antibacterial agents, such as rifampin.[1] Mutations in rpoB that confer resistance to rifamycins do so by altering residues of the rifamycin binding site on RNA polymerase, thereby reducing rifamycin binding affinity for rifamycins[2][3]

Nucleic acid probes can detect mutations in rpoB that confer rifampicin resistance. For Mycobacterium tuberculosis, the rifamycin-resistant mutations most commonly encountered involve codons 516, 526, and 531 (numbered, by convention, as in Escherichia coli rpoB).[4][5] For Staphylococcus aureus, the rifamycin-resistant mutation most commonly encountered involves codon 526.[6]

References

  1. ↑ Floss, H.G.; Yu, T. (2005). "Rifamycin-Mode of Action, Resistance, and Biosynthesis". Chem. Rev. 105 (2): 621–32. doi:10.1021/cr030112j. PMID 15700959.
  2. ↑ Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A. (2001). "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase". Cell 104 (6): 901–12. doi:10.1016/S0092-8674(01)00286-0. PMID 11290327.
  3. ↑ Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., Ebright, R.H. (2008). "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center". Proc Natl Acad Sci USA 105 (39): 14820–5. doi:10.1073/pnas.0802822105. PMC 2567451. PMID 18787125.
  4. ↑ Mokrousov, I.; Otten, T.; Vyshnevskiy, B.; Narvskaya, O. (2003). "Allele-Specific rpoB PCR Assays for Detection of Rifampin-Resistant Mycobacterium tuberculosis in Sputum Smears". Antimicrob Agents Chemother 47 (7): 2231–2235. doi:10.1128/AAC.47.7.2231-2235.2003. PMC 161874. PMID 12821473.
  5. ↑ Telenti A, Imboden P, Marchesi F et al. (1993). "Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis". Lancet 341 (8846): 647–50. doi:10.1016/0140-6736(93)90417-F. PMID 8095569.
  6. ↑ Wichelhaus TA, Schäfer V, Brade V, Böddinghaus B (1999). "Molecular characterization of rpoB mutations conferring cross-resistance to rifamycins on methicillin-resistant Staphylococcus aureus". Antimicrob Agents Chemother 43 (11): 2813–2816. PMC 89569. PMID 10543773.