Arginine homeostasis in J774.1 macrophages in the context of Mycobacterium bovis BCG infection.
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.
Talaue
Meliza T
MT
Department of Microbiology and Molecular Genetics, UMDNJ/ New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Venketaraman
Vishwanath
V
Hazbón
Manzour Hernando
MH
Peteroy-Kelly
Marcy
M
Seth
Anjali
A
Colangeli
Roberto
R
Alland
David
D
Connell
Nancy D
ND
D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D009154:Mutation; D009163:Mycobacterium bovis / Q000254:growth & development; D014380:Tuberculosis, Bovine / Q000378:metabolism* / Q000382:microbiology*
D026923:Amino Acid Transport Systems, Basic; D001426:Bacterial Proteins; D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; C043909:arginine permease; D001120:Arginine