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 Petrella, S.
Right arrow Articles by Sougakoff, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petrella, S.
Right arrow Articles by Sougakoff, W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2006, p. 2853-2856, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.00244-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genetic Basis for Natural and Acquired Resistance to the Diarylquinoline R207910 in Mycobacteria

Stephanie Petrella,1 Emmanuelle Cambau,1 Aurelie Chauffour,1 Koen Andries,2 Vincent Jarlier,1 and Wladimir Sougakoff1*

Laboratoire de Recherche Moléculaire sur les Antibiotiques, LRMA INSERM U655, Université Pierre et Marie Curie, AP-HP CHU Pitié-Salpêtrière, Paris, France,1 Johnson and Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica N.V., Beerse, Belgium2

Received 26 February 2006/ Returned for modification 12 April 2006/ Accepted 1 June 2006

The atpE gene encoding the subunit c of the ATP synthase of Mycobacterium tuberculosis, the target of the new diarylquinoline drug R207910, has been sequenced from in vitro mutants resistant to the drug. The previously reported mutation A63P and a new mutation, I66M, were found. The genetic diversity of atpE in 13 mycobacterial species was also investigated, revealing that the region involved in resistance to R207910 is conserved, except in Mycobacterium xenopi in which the highly conserved residue Ala63 is replaced by Met, a modification that may be associated with the natural resistance of M. xenopi to R207910.

* Corresponding author. Mailing address: L.R.M.A., Laboratoire de Recherche Moléculaire sur les Antibiotiques, Faculté de médecine Pitié-Salpêtrière, 91, boulevard de l'hôpital, F-75634 Paris Cedex 13, France. Phone: 33 (1) 40 77 97 46. Fax: 33 (1) 45 82 75 77. E-mail: sougakof{at}chups.jussieu.fr.

Antimicrobial Agents and Chemotherapy, August 2006, p. 2853-2856, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.00244-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • van den Boogaard, J., Kibiki, G. S., Kisanga, E. R., Boeree, M. J., Aarnoutse, R. E. (2009). New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development. Antimicrob. Agents Chemother. 53: 849-862 [Full Text]  
  • Haagsma, A. C., Abdillahi-Ibrahim, R., Wagner, M. J., Krab, K., Vergauwen, K., Guillemont, J., Andries, K., Lill, H., Koul, A., Bald, D. (2009). Selectivity of TMC207 towards Mycobacterial ATP Synthase Compared with That towards the Eukaryotic Homologue. Antimicrob. Agents Chemother. 53: 1290-1292 [Abstract] [Full Text]  
  • Hong, S., Pedersen, P. L. (2008). ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas. Microbiol. Mol. Biol. Rev. 72: 590-641 [Abstract] [Full Text]  
  • Huitric, E., Verhasselt, P., Andries, K., Hoffner, S. E. (2007). In Vitro Antimycobacterial Spectrum of a Diarylquinoline ATP Synthase Inhibitor. Antimicrob. Agents Chemother. 51: 4202-4204 [Abstract] [Full Text]  
  • Tino, G., Ware, L. B., Moss, M. (2007). Clinical Year in Review IV: Chronic Obstructive Pulmonary Disease, Nonpulmonary Critical Care, Diagnostic Imaging, and Mycobacterial Disease. Proc Am Thorac Soc 4: 494-498 [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»