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Antimicrobial Agents and Chemotherapy, October 2003, p. 3208-3213, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3208-3213.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of Mycobacterium smegmatis and Presence of a Novel Transposon, IS1623

David C. Alexander, Joses R. W. Jones, and Jun Liu*

Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Received 28 May 2003/ Returned for modification 30 June 2003/ Accepted 7 July 2003

Rifampin is a front-line antibiotic for the treatment of tuberculosis. Infections caused by rifampin- and multidrug-resistant Mycobacterium tuberculosis strains are difficult to treat and contribute to a poor clinical outcome. Rifampin resistance most often results from mutations in rpoB. However, some drug-resistant strains have rpoB alleles that encode the phenotype for susceptibility. Similarly, non-M. tuberculosis mycobacteria exhibit higher levels of baseline resistance to rifampin, despite the presence of rpoB alleles that encode the phenotype for susceptibility. To identify other genes involved in rifampin resistance, we generated a library of Mycobacterium smegmatis mc2155 transposon insertion mutants. Upon screening this library, we identified one mutant that was hypersensitive to rifampin. The transposon insertion was localized to the arr gene, which encodes rifampin ADP ribosyltransferase, an enzyme able to inactivate rifampin. Sequence analysis revealed differences in the arr alleles of M. smegmatis strain mc2155 and previously described strain DSM 43756. The arr region of strain mc2155 contains a second, partial copy of the arr gene plus a novel insertion sequence, IS1623.

* Corresponding author. Mailing address: 4382 Medical Sciences Building, Department of Medical Genetics and Microbiology University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Phone: (416) 946-5067. Fax: (416) 978-6885. E-mail: jun.liu{at}utoronto.ca.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3208-3213, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3208-3213.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Baysarowich, J., Koteva, K., Hughes, D. W., Ejim, L., Griffiths, E., Zhang, K., Junop, M., Wright, G. D. (2008). Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr. Proc. Natl. Acad. Sci. USA 105: 4886-4891 [Abstract] [Full Text]  
  • Chen, J. M., German, G. J., Alexander, D. C., Ren, H., Tan, T., Liu, J. (2006). Roles of Lsr2 in Colony Morphology and Biofilm Formation of Mycobacterium smegmatis. J. Bacteriol. 188: 633-641 [Abstract] [Full Text]  
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