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Infection and Immunity, August 2002, p. 4124-4131, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4124-4131.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Disruption of the Gene Homologous to Mammalian Nramp1 in Mycobacterium tuberculosis Does Not Affect Virulence in Mice

Neio Boechat,1,2 Béatrice Lagier-Roger,1,2 Stéphanie Petit,1,2,{dagger} Yann Bordat,1 Jean Rauzier,1 Allan J. Hance,2 Brigitte Gicquel,1 and Jean-Marc Reyrat1*

Unité de Génétique Mycobactérienne, Institut Pasteur,1 INSERM U552, Faculté de Médecine Xavier Bichat, Hôpital Bichat-Claude Bernard, Paris, France2

Received 13 August 2001/ Returned for modification 16 October 2001/ Accepted 29 April 2002

Natural-resistance-associated macrophage protein 1 (Nramp1) is a divalent cation transporter belonging to a family of transporter proteins highly conserved in eukaryotes and prokaryotes. Mammalian and bacterial transporters may compete for essential metal ions during mycobacterial infections. The mycobacterial Nramp homolog may therefore be involved in Mycobacterium tuberculosis virulence. Here, we investigated this possibility by inactivating the M. tuberculosis Nramp1 gene (Mramp) by allelic exchange mutagenesis. Disruption of Mramp did not affect the extracellular growth of bacteria under standard conditions. However, the Mramp mutation was associated with growth impairment under conditions of limited iron availability. The Mramp mutant displayed no impairment of growth or survival in macrophages derived from mouse bone marrow or in Nramp1+/+ and Nramp1-/- congenic murine macrophage cell lines. Following intravenous challenge in BALB/c mice, counts of parental and Mramp mutant strains were similar in the lungs and spleens of the animals at all time points studied. These results indicate that Mramp does not contribute to the virulence of M. tuberculosis in mice.

* Corresponding author. Mailing address: Unité de Génétique Mycobactérienne Institut Pasteur 25, rue du Docteur Roux, 75724 Paris Cédex 15, France. Phone: 33 1 40613274. Fax: 33 1 45688843. E-mail: jmreyrat{at}pasteur.fr.

Editor: S. H. E. Kaufmann

{dagger} Deceased.

Infection and Immunity, August 2002, p. 4124-4131, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4124-4131.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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