Research Highlights

Recruit the transporter and get Arginine-Pathogen uses interesting strategy to get essential amino acid Arginine from the host

- Priyanka Das, Amit Lahiri, Dipshikha Chakravortty, MCBL

Cationic amino acid transporters (mCAT1 and mCAT2B) regulate the arginine availability in macrophages. Little is known how in the infected cell a pathogen can alter the arginine metabolism of the host. We reveal here a novel mechanism by which Salmonella exploit mCAT1 and mCAT2B to acquire host arginine towards its own intracellular growth within antigen presenting cells. We demonstrate that Salmonella infected bone marrow derived macrophages and dendritic cells show enhanced arginine uptake and increased expression of mCAT1 and mCAT2B1. We show that the mCAT1 transporter is in close proximity to Salmonella containing vacuole (SCV) specifically by live intracellular Salmonella in order to access the macrophage cytosolic arginine pool. Further, Lysosome associated membrane protein 1, a marker of SCV, also was found to colocalize with mCAT1 in the Salmonella infected cell. The intra vacuolar Salmonella then acquire the host arginine via its own arginine transporter, ArgT for growth. The argT knockout strain was unable to acquire host arginine and was attenuated in growth in both macrophages and in mice model of infection. Briefly, Salmonella infection increases the arginine transporters and the transporters get localized to the SCV. All these mechanisms lead to the uptake of arginine by the bacteria. In this manner, Salmonella quenches arginine away from the iNOS pathway. In addition, the bacteria acquire arginine for their own protein synthesis at no extra cost. Our data indicates that the arginine tagged antibiotic might facilitate specific and targeted delivery of any antibiotic to intracellular Salmonella and Mycobacteria enabling better killing.

[1] Das P, Lahiri A, Lahiri A, Sen M, Iyer N, Kapoor N, Balaji KN, Chakravortty D.
Cationic Amino Acid Transporters and Salmonella Typhimurium ArgT Collectively Regulate
Arginine Availability towards Intracellular Salmonella Growth. PLoS One. 2010 Dec 3;5(12):