Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1979 Jan;137(1):374–383. doi: 10.1128/jb.137.1.374-383.1979

Genetic analysis of Staphylococcus aureus RNA polymerase mutants.

T O Morrow, S A Harmon
PMCID: PMC218460  PMID: 33150

Abstract

Spontaneous mutants of Staphylococcus aureus resistant to rifampin, rifamycin SV, streptovaricin, or streptolydigin were isolated and shown to be resistant due to chromosomal rather than plasmid mutations. Based on data concerning spontaneous mutation rates, genetic cotransduction rates, and in vitro sensitivity studies, four major antibiotic cross-resistance patterns were found. The genetic markers responsible for these cross-resistance patterns were shown to be separable by transduction. Nonpurified RNA polymerase activity in lysates of mutants showed the same sensitivity to these antibiotics as shown by the mutants on solid media. A model is proposed explaining possible structure-function relationships involved in the binding of these antibiotics to the RNA polymerase molecule and the mutations resulting in resistance to these antibiotics. This model includes generally overlapping but different-sized binding sites on the RNA polymerase protein coded for by similarly arranged mutable sites on the DNA.

Full text

PDF
374

Selected References

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

  1. ARBER W. Transduction of chromosomal genes and episomes in Escherichia coli. Virology. 1960 May;11:273–288. doi: 10.1016/0042-6822(60)90066-0. [DOI] [PubMed] [Google Scholar]
  2. Asheshov E. H. Chromosomal location of the genetic elements controlling penicillinase production in a strain of Staphylococcus aureus. Nature. 1966 May 21;210(5038):804–806. doi: 10.1038/210804a0. [DOI] [PubMed] [Google Scholar]
  3. Binda G., Domenichini E., Gottardi A., Orlandi B., Ortelli E., Pacini B., Fowst G. Rifampicin, a general review. Arzneimittelforschung. 1971 Dec;21(12):1907–1977. [PubMed] [Google Scholar]
  4. Cassani G., Burgess R. R., Goodman H. M., Gold L. Inhibition of RNA polymerase by streptolydigin. Nat New Biol. 1971 Apr 14;230(15):197–200. doi: 10.1038/newbio230197a0. [DOI] [PubMed] [Google Scholar]
  5. Chamberlin M. J., Ring J. Characterization of T7 specific RNA polymerase. 3. Inhibition by derivatives of rifamycin SV. Biochem Biophys Res Commun. 1972 Nov 15;49(4):1129–1136. doi: 10.1016/0006-291x(72)90330-0. [DOI] [PubMed] [Google Scholar]
  6. Haworth S. R., Brown L. R. Genetic analysis of ribonucleic acid polymerase mutants of Bacillus subtilis. J Bacteriol. 1973 Apr;114(1):103–113. doi: 10.1128/jb.114.1.103-113.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heil A., Zillig W. Reconstitution of bacterial DNA-dependent RNA-polymerase from isolated subunits as a tool for the elucidation of the role of the subunits in transcription. FEBS Lett. 1970 Dec;11(3):165–168. doi: 10.1016/0014-5793(70)80519-1. [DOI] [PubMed] [Google Scholar]
  8. Hicks J. B., Herskowitz I. Evidence for a new diffusible element of mating pheromones in yeast. Nature. 1976 Mar 18;260(5548):246–248. doi: 10.1038/260246a0. [DOI] [PubMed] [Google Scholar]
  9. Hui J., Gordon N., Kajioka R. Permeability barrier to rifampin in mycobacteria. Antimicrob Agents Chemother. 1977 May;11(5):773–779. doi: 10.1128/aac.11.5.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Iwakura Y., Ishihama A., Yura T. RNA polymerase mutants of Escherichia coli. Streptolydigin resistance and its relation to rifampicin resistance. Mol Gen Genet. 1973 Mar 1;121(2):181–196. doi: 10.1007/BF00277531. [DOI] [PubMed] [Google Scholar]
  11. LEDERBERG J., LEDERBERG E. M. Replica plating and indirect selection of bacterial mutants. J Bacteriol. 1952 Mar;63(3):399–406. doi: 10.1128/jb.63.3.399-406.1952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mindlin S. Z., Ilyina T. S., Voeykova T. A., Velkov V. V. Genetical analysis of rifampicin resistant mutants of E. coli K 12. Mol Gen Genet. 1972;115(2):115–121. doi: 10.1007/BF00277290. [DOI] [PubMed] [Google Scholar]
  14. Mizuno S., Yamazaki H., Nitta K., Umezawa H. Inhibition of initiation of DNA-dependent RNA synthesis by an antibiotic B44p. Biochem Biophys Res Commun. 1968 Feb 26;30(4):379–385. doi: 10.1016/0006-291x(68)90755-9. [DOI] [PubMed] [Google Scholar]
  15. PATTEE P. A., BALDWIN J. N. Transduction of resistance to chlortetracycline and novobiocin in Staphylococcus aureus. J Bacteriol. 1961 Dec;82:875–881. doi: 10.1128/jb.82.6.875-881.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Poston S. M. Cellular location of the genes controlling penicillinase production and resistance to streptomycin and tetracycline in a strain of Staphylococcus aureus. Nature. 1966 May 21;210(5038):802–804. doi: 10.1038/210802a0. [DOI] [PubMed] [Google Scholar]
  17. SIMINOFF P., SMITH R. M., SOKOLSKI W. T., SAVAGE G. M. Streptovaricin. I. Discovery and biologic activity. Am Rev Tuberc. 1957 Apr;75(4):576–583. doi: 10.1164/artpd.1957.75.4.576. [DOI] [PubMed] [Google Scholar]
  18. Sarubbi F. A., Jr, Blackman E., Sparling P. F. Genetic mapping of linked antibiotic resistance loci in Neisseria gonorrhoeae. J Bacteriol. 1974 Dec;120(3):1284–1292. doi: 10.1128/jb.120.3.1284-1292.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Siddhikol C., Erbstoeszer J. W., Weisblum B. Mode of action of streptolydigin. J Bacteriol. 1969 Jul;99(1):151–155. doi: 10.1128/jb.99.1.151-155.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stender W., Scheit K. H. Studies of the topography of the binding site of DNA-dependent RNA polymerase from Escherichia coli for the antibiotic rifamycin SV. Eur J Biochem. 1977 Jun 15;76(2):591–600. doi: 10.1111/j.1432-1033.1977.tb11629.x. [DOI] [PubMed] [Google Scholar]
  21. Tsukamura M. The pattern of resistance development to rifampicin in Mycobacterium tuberculosis. Tubercle. 1972 Jun;53(2):111–117. doi: 10.1016/0041-3879(72)90027-x. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Wehrli W., Staehelin M. Actions of the rifamycins. Bacteriol Rev. 1971 Sep;35(3):290–309. doi: 10.1128/br.35.3.290-309.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES