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 Gordhan, B. G.
Right arrow Articles by Mizrahi, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gordhan, B. G.
Right arrow Articles by Mizrahi, V.

 Previous Article  |  Next Article 

Infection and Immunity, June 2002, p. 3080-3084, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.3080-3084.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Construction and Phenotypic Characterization of an Auxotrophic Mutant of Mycobacterium tuberculosis Defective in L-Arginine Biosynthesis

Bhavna G. Gordhan,1 Debbie A. Smith,2 Heidi Alderton,2 Ruth A. McAdam,3 Gregory J. Bancroft,2 and Valerie Mizrahi1*

MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, School of Pathology, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa and,1 Immunology Unit, London School of Hygiene & Tropical Medicine, London,2 and Respiratory Pathogens, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom3

Received 1 October 2001/ Returned for modification 22 November 2001/ Accepted 15 March 2002

A mutant of Mycobacterium tuberculosis defective in the metabolism of L-arginine was constructed by allelic exchange mutagenesis. The argF mutant strain required exogenous L-arginine for growth in vitro, and in the presence of 0.96 mM L-arginine, it achieved a growth rate and cell density in stationary phase comparable to those of the wild type. The mutant strain was also able to grow in the presence of high concentrations of argininosuccinate, but its auxotrophic phenotype could not be rescued by L-citrulline, suggesting that the {Delta}argF::hyg mutation exerted a polar effect on the downstream argG gene but not on argH. The mutant strain displayed reduced virulence in immunodeficient SCID mice and was highly attenuated in immunocompetent DBA/2 mice, suggesting that L-arginine availability is restricted in vivo.

* Corresponding author. Mailing address: MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, NHLS (SAIMR), P.O. Box 1038, Johannesburg 2000, South Africa. Phone: 2711 4899370. Fax: 2711 4899001. E-mail: 075val{at}chiron.wits.ac.za.

Editor: S. H. E. Kaufmann

Infection and Immunity, June 2002, p. 3080-3084, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.3080-3084.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mehra, S., Kaushal, D. (2009). Functional Genomics Reveals Extended Roles of the Mycobacterium tuberculosis Stress Response Factor {sigma}H. J. Bacteriol. 191: 3965-3980 [Abstract] [Full Text]  
  • Napolitano, D. R., Pollock, N., Kashino, S. S., Rodrigues, V. Jr., Campos-Neto, A. (2008). Identification of Mycobacterium tuberculosis Ornithine Carboamyltransferase in Urine as a Possible Molecular Marker of Active Pulmonary Tuberculosis. CVI 15: 638-643 [Abstract] [Full Text]  
  • Warner, D. F., Savvi, S., Mizrahi, V., Dawes, S. S. (2007). A Riboswitch Regulates Expression of the Coenzyme B12-Independent Methionine Synthase in Mycobacterium tuberculosis: Implications for Differential Methionine Synthase Function in Strains H37Rv and CDC1551. J. Bacteriol. 189: 3655-3659 [Abstract] [Full Text]  
  • Talaue, M. T., Venketaraman, V., Hazbon, M. H., Peteroy-Kelly, M., Seth, A., Colangeli, R., Alland, D., Connell, N. D. (2006). Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection. J. Bacteriol. 188: 4830-4840 [Abstract] [Full Text]  
  • Prakash, P., Aruna, B., Sardesai, A. A., Hasnain, S. E. (2005). Purified Recombinant Hypothetical Protein Coded by Open Reading Frame Rv1885c of Mycobacterium tuberculosis Exhibits a Monofunctional AroQ Class of Periplasmic Chorismate Mutase Activity. J. Biol. Chem. 280: 19641-19648 [Abstract] [Full Text]  
  • Errey, J. C., Blanchard, J. S. (2005). Functional Characterization of a Novel ArgA from Mycobacterium tuberculosis. J. Bacteriol. 187: 3039-3044 [Abstract] [Full Text]  
  • Parish, T. (2003). Starvation Survival Response of Mycobacterium tuberculosis. J. Bacteriol. 185: 6702-6706 [Abstract] [Full Text]  
  • Sassetti, C. M., Rubin, E. J. (2003). Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA 100: 12989-12994 [Abstract] [Full Text]  
  • Tullius, M. V., Harth, G., Horwitz, M. A. (2003). Glutamine Synthetase GlnA1 Is Essential for Growth of Mycobacterium tuberculosis in Human THP-1 Macrophages and Guinea Pigs. Infect. Immun. 71: 3927-3936 [Abstract] [Full Text]  
  • Parish, T., Smith, D. A., Kendall, S., Casali, N., Bancroft, G. J., Stoker, N. G. (2003). Deletion of Two-Component Regulatory Systems Increases the Virulence of Mycobacterium tuberculosis. Infect. Immun. 71: 1134-1140 [Abstract] [Full Text]  
  • McAdam, R. A., Quan, S., Smith, D. A., Bardarov, S., Betts, J. C., Cook, F. C., Hooker, E. U., Lewis, A. P., Woollard, P., Everett, M. J., Lukey, P. T., Bancroft, G. J., Jacobs, W. R. Jr, Duncan, K. (2002). Characterization of a Mycobacterium tuberculosis H37Rv transposon library reveals insertions in 351 ORFs and mutants with altered virulence. Microbiology 148: 2975-2986 [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»