rpoB

The rpoB gene encodes the β subunit of bacterial RNA polymerase. It codes for 1342 amino acids, making it the second-largest polypeptide in the bacterial cell.[1] It is the site of mutations that confer resistance to the rifamycin antibacterial agents, such as rifampin.[2] 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[3][4]

Initial studies were done by Jin and Gross to generate rpoB mutations in E. coli that conferred resistance to rifampicin. Three clusters of mutations were identified, cluster I at codons 507-533, cluster II at codons 563-572, and cluster III at codon 687.[1][5]

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).[6][7] For Staphylococcus aureus, the rifamycin-resistant mutation most commonly encountered involves codon 526.[8]

References

  1. 1 2 Goldstein, Beth P. "Resistance to rifampicin: a review". The Journal of Antibiotics. 67 (9): 625–630. doi:10.1038/ja.2014.107.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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 2567451Freely accessible. PMID 18787125.
  5. ↑ Jin, Ding Jun; Gross, Carol A. (1988-07-05). "Mapping and sequencing of mutations in the Escherichia colirpoB gene that lead to rifampicin resistance". Journal of Molecular Biology. 202 (1): 45–58. doi:10.1016/0022-2836(88)90517-7.
  6. ↑ 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 161874Freely accessible. PMID 12821473.
  7. ↑ 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.
  8. ↑ 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 89569Freely accessible. PMID 10543773.
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