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Journal of Bacteriology, July 2006, p. 4830-4840, Vol. 188, No. 13
0021-9193/06/$08.00+0     doi:10.1128/JB.01687-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

Meliza T. Talaue,^1,2 Vishwanath Venketaraman,² Manzour Hernando Hazbón,² Marcy Peteroy-Kelly,⁴ Anjali Seth,³ Roberto Colangeli,² David Alland,² and Nancy D. Connell^1,2*

Department of Microbiology and Molecular Genetics,¹ Department of Medicine,² Department of Biochemistry and Molecular Biology, UMDNJ/New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103-2714,³ Pace University, 1 Pace Plaza, New York, New York 10038⁴

Received 5 November 2005/ Accepted 12 April 2006

The competition for L-arginine between the inducible nitric oxide synthase and arginase contributes to the outcome of several parasitic and bacterial infections. The acquisition of L-arginine, however, is important not only for the host cells but also for the intracellular pathogen. In this study we observe that strain AS-1, the Mycobacterium bovis BCG strain lacking the Rv0522 gene, which encodes an arginine permease, perturbs L-arginine metabolism in J774.1 murine macrophages. Infection with AS-1, but not with wild-type BCG, induced L-arginine uptake in J774.1 cells. This increase in L-arginine uptake was independent of activation with gamma interferon plus lipopolysaccharide and correlated with increased expression of the MCAT1 and MCAT2 cationic amino acid transport genes. AS-1 infection also enhanced arginase activity in resting J774.1 cells. Survival studies revealed that AS-1 survived better than BCG within resting J774.1 cells. Intracellular growth of AS-1 was further enhanced by inhibiting arginase and ornithine decarboxylase activities in J774.1 cells using L-norvaline and difluoromethylornithine treatment, respectively. These results suggest that the arginine-related activities of J774.1 macrophages are affected by the arginine transport capacity of the infecting BCG strain. The loss of Rv0522 gene-encoded arginine transport may have induced other cationic amino acid transport systems during intracellular growth of AS-1, allowing better survival within resting macrophages.

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* Corresponding author. Mailing address: Department of Medicine, UMDNJ/New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714. Phone: (973) 972-3759. Fax: (973) 972-3644. E-mail: connell{at}umdnj.edu.

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Journal of Bacteriology, July 2006, p. 4830-4840, Vol. 188, No. 13
0021-9193/06/$08.00+0     doi:10.1128/JB.01687-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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