Skip to main content
PMC home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1971 Nov;108(2):737–741. doi: 10.1128/jb.108.2.737-741.1971

Mechanism of Action of Rifampin on Mycobacterium smegmatis

R J White 1, G C Lancini 1, L G Silvestri 1
PMCID: PMC247133  PMID: 4942761

Abstract

Deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase (EC 2.7.7.6) isolated from a rifampin-sensitive strain of Mycobacterium smegmatis was 90% inhibited by 1 μg of rifampin per ml; enzyme from a rifampin-resistant mutant was not affected by this concentration of antibiotic. Inhibition of phenylalanine-1-14C incorporation by rifampin in growing cultures was complete about 6 min after addition of antibiotic. Under the same conditions, uracil-2-14c incorporated was blocked after 1.5 to 2 min. Rifampin kills M. smegmatis very slowly. When rifampin-inhibited cultures were transferred to a rifampin-free medium, there was a partial resumption of uracil-2-14C incorporation, even in the presence of chloramphenicol. We conclude that a primary event in the inhibition of M. smegmatis by rifampin is the block of DNA-dependent RNA polymerase.

Full text

PDF
737

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arioli V., Pallanza R., Furesz S., Carniti G. Rifampicin: a new rifamycin. I. Bacteriological studies. Arzneimittelforschung. 1967 May;17(5):523–529. [PubMed] [Google Scholar]
  2. Burgess R. R. A new method for the large scale purification of Escherichia coli deoxyribonucleic acid-dependent ribonucleic acid polymerase. J Biol Chem. 1969 Nov 25;244(22):6160–6167. [PubMed] [Google Scholar]
  3. Doi R. H., Brown L. R., Rodgers G., Hsu Y. Bacillus subtilis mutant altered in spore morphology and in RNA polymerase activity. Proc Natl Acad Sci U S A. 1970 Jun;66(2):404–410. doi: 10.1073/pnas.66.2.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ezekiel D. H., Hutchins J. E. Mutations affecting RNA polymerase associated with rifampicin resistance in Escherichia coli. Nature. 1968 Oct 19;220(5164):276–277. doi: 10.1038/220276a0. [DOI] [PubMed] [Google Scholar]
  5. Gray W. J., Midgley J. E. The control of ribonucleic acid synthesis in bacteria. The synthesis and stbility of ribonucleic acid in rifampicin-inhibited cultures of Escherichia coli. Biochem J. 1971 Apr;122(2):161–169. doi: 10.1042/bj1220161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hartmann G., Honikel K. O., Knüsel F., Nüesch J. The specific inhibition of the DNA-directed RNA synthesis by rifamycin. Biochim Biophys Acta. 1967;145(3):843–844. doi: 10.1016/0005-2787(67)90147-5. [DOI] [PubMed] [Google Scholar]
  7. Lancini G. C., Sartori G. Rifamycins LXI: in vivo inhibition of RNA synthesis of rifamycins. Experientia. 1968 Nov 15;24(11):1105–1106. doi: 10.1007/BF02147783. [DOI] [PubMed] [Google Scholar]
  8. Lancini G., Pallanza R., Silvestri L. G. Relationships between bactericidal effect and inhibition of ribonucleic acid nucleotidyltransferase by rifampicin in Escherichia coli K-12. J Bacteriol. 1969 Feb;97(2):761–768. doi: 10.1128/jb.97.2.761-768.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pallanza R., Arioli V., Furesz S., Bolzoni G. Rifampicin: a new rifamycin. II. Laboratory studies on the antituberculous activity and preliminary clinical observations. Arzneimittelforschung. 1967 May;17(5):529–534. [PubMed] [Google Scholar]
  10. Rabussay D., Zillig W. A rifampicin resistent rna-polymerase from E. coli altered in the beta-subunit. FEBS Lett. 1969 Oct 21;5(2):104–106. doi: 10.1016/0014-5793(69)80305-4. [DOI] [PubMed] [Google Scholar]
  11. Rees R. J., Pearson J. M., Waters M. F. Experimental and clinical studies on rifampicin in treatment of leprosy. Br Med J. 1970 Jan 10;1(5688):89–92. doi: 10.1136/bmj.1.5688.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Reid P., Speyer J. Rifampicin inhibition of ribonucleic acid and protein synthesis in normal and ethylenediaminetetraacetic acid-treated Escherichia coli. J Bacteriol. 1970 Oct;104(1):376–389. doi: 10.1128/jb.104.1.376-389.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. SENSI P., MARGALITH P., TIMBAL M. T. Rifomycin, a new antibiotic; preliminary report. Farmaco Sci. 1959;14(2):146–147. [PubMed] [Google Scholar]
  14. Sonenshein A. L., Losick R. RNA polymerase mutants blocked in sporulation. Nature. 1970 Aug 29;227(5261):906–909. doi: 10.1038/227906a0. [DOI] [PubMed] [Google Scholar]
  15. Tocchini-Valentini G. P., Marino P., Colvill A. J. Mutant of E. coli containing an altered DNA-dependent RNA polymerase. Nature. 1968 Oct 19;220(5164):275–276. doi: 10.1038/220275a0. [DOI] [PubMed] [Google Scholar]
  16. Wehrli W., Knüsel F., Staehelin M. Action of rifamycin on RNA-polymerase from sensitive and resistant bacteria. Biochem Biophys Res Commun. 1968 Jul 26;32(2):284–288. doi: 10.1016/0006-291x(68)90382-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES