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 Nash, K. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nash, K. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2003, p. 3053-3060, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3053-3060.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Intrinsic Macrolide Resistance in Mycobacterium smegmatis Is Conferred by a Novel erm Gene, erm(38)

Kevin A. Nash*

Children's Hospital Los Angeles and University of Southern California, Los Angeles, California

Received 24 March 2003/ Returned for modification 29 April 2003/ Accepted 30 June 2003

High-level, acquired macrolide resistance in mycobacteria is conferred by mutation within the 23S rRNA gene. However, several mycobacteria are naturally resistant to macrolides, including the Mycobacterium smegmatis group and Mycobacterium tuberculosis complex. Thus, the aim of this study was to characterize this resistance. Intrinsic macrolide resistance in M. smegmatis was inducible and showed cross-resistance to lincosamides but not to streptogramin B (i.e., ML resistance). A similar phenotype was found with Mycobacterium microti and macrolide-resistant Mycobacterium fortuitum. A search of the DNA sequence data for M. smegmatis strain mc2155 identified a novel erm gene, erm(38), and expression analysis showed that erm(38) RNA levels increased >10-fold after a 2-h incubation with macrolide. Inducible ML resistance was not expressed by an erm(38) knockout mutant, and complementation of this mutant with intact erm(38) in trans resulted in high-level ML resistance (e.g., clarithromycin MIC of >512 µg/ml). Thus, the results indicate that erm(38) confers the intrinsic ML resistance of M. smegmatis. Southern blot analysis with an erm(38)-specific probe indicated that a similar gene may be present in macrolide-resistant M. fortuitum. This finding, with the presence of the erm(37) gene (Rv1988) in the M. tuberculosis complex, suggests that such genes are widespread in mycobacteria with intrinsic macrolide resistance.

* Mailing address: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd., Mailstop 103, Los Angeles, CA 90027. Phone: (323) 669-5670. Fax: (323) 666-7681. E-mail: kanash{at}usc.edu.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3053-3060, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3053-3060.2003
Copyright © 2003, 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]  
  • Griffith, D. E., Aksamit, T., Brown-Elliott, B. A., Catanzaro, A., Daley, C., Gordin, F., Holland, S. M., Horsburgh, R., Huitt, G., Iademarco, M. F., Iseman, M., Olivier, K., Ruoss, S., von Reyn, C. F., Wallace, R. J. Jr., Winthrop, K., on behalf of the ATS Mycobacterial Diseases Subcom, (2007). An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. Am. J. Respir. Crit. Care Med. 175: 367-416 [Full Text]  
  • Nash, K. A., Andini, N., Zhang, Y., Brown-Elliott, B. A., Wallace, R. J. Jr. (2006). Intrinsic macrolide resistance in rapidly growing mycobacteria.. Antimicrob. Agents Chemother. 50: 3476-3478 [Abstract] [Full Text]  
  • Andini, N., Nash, K. A. (2006). Intrinsic Macrolide Resistance of the Mycobacterium tuberculosis Complex Is Inducible.. Antimicrob. Agents Chemother. 50: 2560-2562 [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]  
  • Pfister, P., Corti, N., Hobbie, S., Bruell, C., Zarivach, R., Yonath, A., Bottger, E. C. (2005). 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A->G. Proc. Natl. Acad. Sci. USA 102: 5180-5185 [Abstract] [Full Text]  
  • Nash, K. A., Zhang, Y., Brown-Elliott, B. A., Wallace, R. J. Jr (2005). Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother 55: 170-177 [Abstract] [Full Text]  
  • Philalay, J. S., Palermo, C. O., Hauge, K. A., Rustad, T. R., Cangelosi, G. A. (2004). Genes Required for Intrinsic Multidrug Resistance in Mycobacterium avium. Antimicrob. Agents Chemother. 48: 3412-3418 [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»