This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, M.
Right arrow Articles by Douthwaite, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, M.
Right arrow Articles by Douthwaite, S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2002, p. 1629-1633, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1629-1633.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Activity of the Ketolide Telithromycin Is Refractory to Erm Monomethylation of Bacterial rRNA

Mingfu Liu and Stephen Douthwaite*

Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark

Received 18 July 2001/ Returned for modification 18 November 2001/ Accepted 7 February 2002

Methylation of specific nucleotides in rRNA is one of the means by which bacteria achieve resistance to macrolides-lincosamides-streptogramin B (MLSB) and ketolide antibiotics. The degree of resistance is determined by how effectively the rRNA is methylated. We have implemented a bacterial system in which the rRNA methylations are defined, and in this study we investigate what effect Erm mono- and dimethylation of the rRNA has on the activity of representative MLSB and ketolide antibiotics. In the test system, >80% of the rRNA molecules are monomethylated by ErmN (TlrD) or dimethylated by ErmE. ErmE dimethylation confers high resistance to all the MLSB and ketolide drugs. ErmN monomethylation predictably confers high resistance to the lincosamides clindamycin and lincomycin, intermediate resistance to the macrolides clarithromycin and erythromycin, and low resistance to the streptogramin B pristinamycin IA. In contrast to the macrolides, monomethylation only mildly affects the antimicrobial activities of the ketolides HMR 3647 (telithromycin) and HMR 3004, and these drugs remain 16 to 250 times as potent as clarithromycin and erythromycin. These differences in the macrolide and ketolide activities could explain the recent reports of variation in the MICs of telithromycin for streptococcal strains that have constitutive erm MLSB resistance and are highly resistant to erythromycin.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark. Phone: (45) 65 50 23 95. Fax: (45) 65 50 24 67. E-mail: srd{at}bmb.sdu.dk.

Antimicrobial Agents and Chemotherapy, June 2002, p. 1629-1633, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1629-1633.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nash, K. A., Brown-Elliott, B. A., Wallace, R. J. Jr. (2009). A Novel Gene, erm(41), Confers Inducible Macrolide Resistance to Clinical Isolates of Mycobacterium abscessus but Is Absent from Mycobacterium chelonae. Antimicrob. Agents Chemother. 53: 1367-1376 [Abstract] [Full Text]  
  • Wolter, N., Smith, A. M., Farrell, D. J., Northwood, J. B., Douthwaite, S., Klugman, K. P. (2008). Telithromycin Resistance in Streptococcus pneumoniae Is Conferred by a Deletion in the Leader Sequence of erm(B) That Increases rRNA Methylation. Antimicrob. Agents Chemother. 52: 435-440 [Abstract] [Full Text]  
  • Dreier, J., Amantea, E., Kellenberger, L., Page, M. G. P. (2007). Activity of the Novel Macrolide BAL19403 against Ribosomes from Erythromycin-Resistant Propionibacterium acnes. Antimicrob. Agents Chemother. 51: 4361-4365 [Abstract] [Full Text]  
  • Wolter, N., Smith, A. M., Low, D. E., Klugman, K. P. (2007). High-Level Telithromycin Resistance in a Clinical Isolate of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51: 1092-1095 [Abstract] [Full Text]  
  • Madsen, C. T., Jakobsen, L., Buriankova, K., Doucet-Populaire, F., Pernodet, J.-L., Douthwaite, S. (2005). Methyltransferase Erm(37) Slips on rRNA to Confer Atypical Resistance in Mycobacterium tuberculosis. J. Biol. Chem. 280: 38942-38947 [Abstract] [Full Text]  
  • Madsen, C. T., Jakobsen, L., Douthwaite, S. (2005). Mycobacterium smegmatis Erm(38) Is a Reluctant Dimethyltransferase. Antimicrob. Agents Chemother. 49: 3803-3809 [Abstract] [Full Text]  
  • Peiru, S., Menzella, H. G., Rodriguez, E., Carney, J., Gramajo, H. (2005). Production of the Potent Antibacterial Polyketide Erythromycin C in Escherichia coli. Appl. Environ. Microbiol. 71: 2539-2547 [Abstract] [Full Text]  
  • LIU, M., NOVOTNY, G. W., DOUTHWAITE, S. (2004). Methylation of 23S rRNA nucleotide G745 is a secondary function of the RlmAI methyltransferase. RNA 10: 1713-1720 [Abstract] [Full Text]  
  • Novotny, G. W., Jakobsen, L., Andersen, N. M., Poehlsgaard, J., Douthwaite, S. (2004). Ketolide Antimicrobial Activity Persists after Disruption of Interactions with Domain II of 23S rRNA. Antimicrob. Agents Chemother. 48: 3677-3683 [Abstract] [Full Text]  
  • Drago, L., De Vecchi, E., Nicola, L., Colombo, A., Gismondo, M. R. (2004). Selection of resistance of telithromycin against Haemophilus influenzae, Moraxella catarrhalis and streptococci in comparison with macrolides. J Antimicrob Chemother 54: 542-545 [Abstract] [Full Text]  
  • Reinert, R. R. (2004). Clinical efficacy of ketolides in the treatment of respiratory tract infections. J Antimicrob Chemother 53: 918-927 [Abstract] [Full Text]  
  • Buriankova, K., Doucet-Populaire, F., Dorson, O., Gondran, A., Ghnassia, J.-C., Weiser, J., Pernodet, J.-L. (2004). Molecular Basis of Intrinsic Macrolide Resistance in the Mycobacterium tuberculosis Complex. Antimicrob. Agents Chemother. 48: 143-150 [Abstract] [Full Text]  
  • Nash, K. A. (2003). Intrinsic Macrolide Resistance in Mycobacterium smegmatis Is Conferred by a Novel erm Gene, erm(38). Antimicrob. Agents Chemother. 47: 3053-3060 [Abstract] [Full Text]  
  • Walsh, F., Willcock, J., Amyes, S. (2003). High-level telithromycin resistance in laboratory-generated mutants of Streptococcus pneumoniae. J Antimicrob Chemother 52: 345-353 [Abstract] [Full Text]  
  • Berisio, R., Harms, J., Schluenzen, F., Zarivach, R., Hansen, H. A. S., Fucini, P., Yonath, A. (2003). Structural Insight into the Antibiotic Action of Telithromycin against Resistant Mutants. J. Bacteriol. 185: 4276-4279 [Abstract] [Full Text]  
  • Morosini, M.-I., Canton, R., Loza, E., del Campo, R., Almaraz, F., Baquero, F. (2003). Streptococcus pyogenes isolates with characterized macrolide resistance mechanisms in Spain: in vitro activities of telithromycin and cethromycin. J Antimicrob Chemother 52: 50-55 [Abstract] [Full Text]  
  • Ackermann, G., Rodloff, A. C. (2003). Drugs of the 21st century: telithromycin (HMR 3647)--the first ketolide. J Antimicrob Chemother 51: 497-511 [Abstract] [Full Text]  
  • Liu, M., Douthwaite, S. (2002). Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy. Proc. Natl. Acad. Sci. USA 99: 14658-14663 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»