Arginine homeostasis in J774.1 macrophages in the context of Mycobacterium bovis BCG infection

Meliza T. Talaue, Vishwanath Venketaraman, Manzour Hernando Hazbón, Marcy Peteroy-Kelly, Anjali Seth, Roberto Colangeli, David Alland, Nancy D. Connell

Research output: Contribution to journalArticle

Abstract

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 marine 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 belter survival within resting macrophages.

Original languageEnglish (US)
Pages (from-to)4830-4840
Number of pages11
JournalJournal of bacteriology
Volume188
Issue number13
DOIs
StatePublished - Jul 1 2006

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ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Talaue, M. T., Venketaraman, V., Hazbón, 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. Journal of bacteriology, 188(13), 4830-4840. https://doi.org/10.1128/JB.01687-05