Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Feb;38(2):381–384. doi: 10.1128/aac.38.2.381

Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare.

A Meier 1, P Kirschner 1, B Springer 1, V A Steingrube 1, B A Brown 1, R J Wallace Jr 1, E C Böttger 1
PMCID: PMC284463  PMID: 8192472

Abstract

Clarithromycin is a potent macrolide that has been used for treating infections with nontuberculous mycobacteria. Pairs of susceptible and resistant Mycobacterium intracellulare strains were obtained from patients with chronic pulmonary M. intracellulare infections undergoing monotherapy with clarithromycin. Nucleotide sequence comparisons of the peptidyltransferase region in 23S rRNAs from parental and resistant strains revealed that in three of six resistant strains, for which the MIC was > 32 micrograms/ml, a single base was mutated (Escherichia coli equivalent, A-2058-->G, C, or U). As the modification of adenine 2058 by dimethylation is a frequent cause of macrolide resistance in a variety of different bacteria, we suggest that mutation of A-2058 confers acquired resistance to clarithromycin in M. intracellulare.

Full text

PDF
381

Images in this article

Selected References

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

  1. Brown B. A., Wallace R. J., Jr, Onyi G. O. Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system. Antimicrob Agents Chemother. 1992 Sep;36(9):1987–1990. doi: 10.1128/aac.36.9.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown B. A., Wallace R. J., Jr, Onyi G. O., De Rosas V., Wallace R. J., 3rd Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonae-like organisms. Antimicrob Agents Chemother. 1992 Jan;36(1):180–184. doi: 10.1128/aac.36.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dautzenberg B., Truffot C., Legris S., Meyohas M. C., Berlie H. C., Mercat A., Chevret S., Grosset J. Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):564–569. doi: 10.1164/ajrccm/144.3_Pt_1.564. [DOI] [PubMed] [Google Scholar]
  4. Ettayebi M., Prasad S. M., Morgan E. A. Chloramphenicol-erythromycin resistance mutations in a 23S rRNA gene of Escherichia coli. J Bacteriol. 1985 May;162(2):551–557. doi: 10.1128/jb.162.2.551-557.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Finken M., Kirschner P., Meier A., Wrede A., Böttger E. C. Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. Mol Microbiol. 1993 Sep;9(6):1239–1246. doi: 10.1111/j.1365-2958.1993.tb01253.x. [DOI] [PubMed] [Google Scholar]
  6. Gauthier A., Turmel M., Lemieux C. Mapping of chloroplast mutations conferring resistance to antibiotics in Chlamydomonas: evidence for a novel site of streptomycin resistance in the small subunit rRNA. Mol Gen Genet. 1988 Oct;214(2):192–197. doi: 10.1007/BF00337710. [DOI] [PubMed] [Google Scholar]
  7. Harris E. H., Burkhart B. D., Gillham N. W., Boynton J. E. Antibiotic resistance mutations in the chloroplast 16S and 23S rRNA genes of Chlamydomonas reinhardtii: correlation of genetic and physical maps of the chloroplast genome. Genetics. 1989 Oct;123(2):281–292. doi: 10.1093/genetics/123.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heifets L. B., Lindholm-Levy P. J., Comstock R. D. Clarithromycin minimal inhibitory and bactericidal concentrations against Mycobacterium avium. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856–858. doi: 10.1164/ajrccm/145.4_Pt_1.856. [DOI] [PubMed] [Google Scholar]
  9. Ji B., Lounis N., Truffot-Pernot C., Grosset J. Selection of resistant mutants of Mycobacterium avium in beige mice by clarithromycin monotherapy. Antimicrob Agents Chemother. 1992 Dec;36(12):2839–2840. doi: 10.1128/aac.36.12.2839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leclercq R., Courvalin P. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother. 1991 Jul;35(7):1267–1272. doi: 10.1128/aac.35.7.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mazurek G. H., Hartman S., Zhang Y., Brown B. A., Hector J. S., Murphy D., Wallace R. J., Jr Large DNA restriction fragment polymorphism in the Mycobacterium avium-M. intracellulare complex: a potential epidemiologic tool. J Clin Microbiol. 1993 Feb;31(2):390–394. doi: 10.1128/jcm.31.2.390-394.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Meier A., Persing D. H., Finken M., Böttger E. C. Elimination of contaminating DNA within polymerase chain reaction reagents: implications for a general approach to detection of uncultured pathogens. J Clin Microbiol. 1993 Mar;31(3):646–652. doi: 10.1128/jcm.31.3.646-652.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moazed D., Noller H. F. Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA. Biochimie. 1987 Aug;69(8):879–884. doi: 10.1016/0300-9084(87)90215-x. [DOI] [PubMed] [Google Scholar]
  14. Nightingale S. D., Byrd L. T., Southern P. M., Jockusch J. D., Cal S. X., Wynne B. A. Incidence of Mycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients. J Infect Dis. 1992 Jun;165(6):1082–1085. doi: 10.1093/infdis/165.6.1082. [DOI] [PubMed] [Google Scholar]
  15. Noller H. F. Structure of ribosomal RNA. Annu Rev Biochem. 1984;53:119–162. doi: 10.1146/annurev.bi.53.070184.001003. [DOI] [PubMed] [Google Scholar]
  16. Otaka E., Teraoka H., Tamaki M., Tanaka K., Osawa S. Ribosomes from erythromycin-resistant mutants of Escherichia coli Q13. J Mol Biol. 1970 Mar;48(3):499–510. doi: 10.1016/0022-2836(70)90061-6. [DOI] [PubMed] [Google Scholar]
  17. Pernodet J. L., Boccard F., Alegre M. T., Blondelet-Rouault M. H., Guérineau M. Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens. EMBO J. 1988 Jan;7(1):277–282. doi: 10.1002/j.1460-2075.1988.tb02810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ruf B., Schürmann D., Mauch H., Jautzke G., Fehrenbach F. J., Pohle H. D. Effectiveness of the macrolide clarithromycin in the treatment of Mycobacterium avium complex infection in HIV-infected patients. Infection. 1992 Sep-Oct;20(5):267–272. doi: 10.1007/BF01710792. [DOI] [PubMed] [Google Scholar]
  19. Skinner R., Cundliffe E., Schmidt F. J. Site of action of a ribosomal RNA methylase responsible for resistance to erythromycin and other antibiotics. J Biol Chem. 1983 Oct 25;258(20):12702–12706. [PubMed] [Google Scholar]
  20. Sor F., Fukuhara H. Erythromycin and spiramycin resistance mutations of yeast mitochondria: nature of the rib2 locus in the large ribosomal RNA gene. Nucleic Acids Res. 1984 Nov 26;12(22):8313–8318. doi: 10.1093/nar/12.22.8313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sor F., Fukuhara H. Identification of two erythromycin resistance mutations in the mitochondrial gene coding for the large ribosomal RNA in yeast. Nucleic Acids Res. 1982 Nov 11;10(21):6571–6577. doi: 10.1093/nar/10.21.6571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Takata R., Osawa S., Tanaka K., Teraoka H., Tamaki M. Genetic studies of he ribosoml proteis in Escherichaoli. V. Mapp-ing of erythromycin resistance mutations which lea to alteration of a 50s ribosomal protein component. Mol Gen Genet. 1970;109(2):123–130. doi: 10.1007/BF00269648. [DOI] [PubMed] [Google Scholar]
  23. Tanaka K., Tamaki M., Osawa S., Kimura A., Takata R. Erythromycin resistant mutants of Bacillus subtilis. Mol Gen Genet. 1973 Dec 20;127(2):157–161. doi: 10.1007/BF00333663. [DOI] [PubMed] [Google Scholar]
  24. Thompson D. E., Balsdon J. T., Cai J., Collins M. D. Studies on the ribosomal RNA operons of Listeria monocytogenes. FEMS Microbiol Lett. 1992 Sep 15;75(2-3):219–224. doi: 10.1016/0378-1097(92)90407-f. [DOI] [PubMed] [Google Scholar]
  25. Vester B., Garrett R. A. A plasmid-coded and site-directed mutation in Escherichia coli 23S RNA that confers resistance to erythromycin: implications for the mechanism of action of erythromycin. Biochimie. 1987 Aug;69(8):891–900. doi: 10.1016/0300-9084(87)90217-3. [DOI] [PubMed] [Google Scholar]
  26. Weisblum B., Demohn V. Erythromycin-inducible resistance in Staphylococcus aureus: survey of antibiotic classes involved. J Bacteriol. 1969 May;98(2):447–452. doi: 10.1128/jb.98.2.447-452.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wittmann H. G., Stöffler G., Apirion D., Rosen L., Tanaka K., Tamaki M., Takata R., Dekio S., Otaka E. Biochemical and genetic studies on two different types of erythromycin resistant mutants of Escherichia coli with altered ribosomal proteins. Mol Gen Genet. 1973 Dec 20;127(2):175–189. doi: 10.1007/BF00333665. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES