The arginine/ornithine binding protein ArgT plays an essential role in / to prevent intracellular killing and contribute to chronic persistence in the host.

species are facultative intracellular bacterial pathogens that cause the contagious zoonotic disease, brucellosis. spp. infect a wide range of animals, including livestock, wild animals, and marine mammals. Compared with other invasive bacterial pathogens, partial information is available on the virulence factors of that enable them to survive in the host. Here, we performed transposon-based random mutagenesis of and identified the arginine/ornithine binding protein, ArgT, as one of the crucial virulence determinants of . Deleting from or resulted in its attenuation in macrophages, which was restored upon complementation with an expression plasmid. We observed that macrophages infected with Δ produced elevated levels of NO due to the inability of these mutants to deplete the host intracellular arginine through their importer. Furthermore, defective survival of Δ and was observed in the infected mice, which correlated with enhanced NO production in the mice. Our studies revealed that plays a vital role in preventing intracellular killing and contributes to the chronic persistence of in the host. This study highlights the essential role of arginine in clearing intracellular infections and the subversion of this host defense mechanism by intracellular pathogens for their chronic persistence.