Role of branched-chain amino acid transporters in Staphylococcus aureus virulence

Branched-chain amino acids (BCAAs) act as effector molecules that signal a global transcriptional regulator, CodY, to regulate virulence factors in nutrient depleted environments. Staphylococcus aureus contains three putative BCAA transporters (BrnQ1, BrnQ2, BrnQ3) whose role in BCAA uptake is unknown. We hypothesize that BrnQ transporters are involved in BCAA uptake and contribute to virulence in S. aureus by modulating CodY activity. Results from radioactive uptake assays indicate that BrnQ1 is the predominant BrnQ transporter of isoleucine, valine and leucine. Meanwhile, BrnQ2 is more specific for isoleucine. Furthermore, only the lack of BrnQ1 hinders growth of S. aureus in chemically-defined media with limited concentrations of BCAAs; however, BrnQ2 and BrnQ3 show no such growth phenotype. In vivo, the brnQ1 and brnQ3 mutants are attenuated for virulence in a mouse model of bacteremia, but the brnQ2 mutant was hyper-virulent, suggesting that the gene plays a more important role within the host.