ArgT functions as an arginine transporter in <i>Staphylococcus aureus</i>

Glycolytic activity is required for <i>Staphylococcus aureus</i> (<i>S. aureus</i>) to establish an infection. These data indicate that carbon catabolite repression, mediated by CcpA, is active during the initial stages of infection. CcpA represses both the biosynthesis and catabolism of arginine; therefore, it is hypothesized that arginine must be transported by <i>S. aureus</i> from host tissue to facilitate growth during the establishment of an infection. Within <i>S. aureus</i> USA300, two known arginine/ornithine antiporters, ArcD1 and ArcD2, are encoded on the two copies of the arginine deiminase operon (native and arginine catabolite mobile genetic element-derived). However, when both antiporters are inactivated via allelic replacement, no growth defect is observed in defined medium where arginine is required for growth, indicating that <i>S. aureus</i> contains additional arginine transporters. Using the toxic arginine analog, canavanine, we identified a novel <i>S. aureus</i> arginine transporter, SAUSA300_<i>2383</i> (<u>Arg</u>inine <u>T</u>ransporter; ArgT). Transcriptional analysis found that <i>argT</i> was regulated by both the canonical arginine biosynthesis repressor AhrC and CcpA; thus, its transcription is repressed during growth in medium containing glucose and is therefore not the primary arginine transporter during growth in medium containing glucose. However, we found that growth is dependent upon ArgT during growth in medium lacking proline, which suggests that <i>S. aureus</i> has evolved a specific response to accommodate proline-depleted growth conditions.IMPORTANCE<i>Staphylococcus aureus</i> is a leading cause of both community and hospital-acquired infection worldwide. In addition, <i>S. aureus</i> is resistant to many commonly used antibiotics, which make the treatment of bacteremia, infective endocarditis, and other invasive diseases more challenging. It is essential to obtain a basic understanding of how <i>S. aureus</i> survives in a variety of host niches, including those niches where <i>S. aureus</i> is dependent upon amino acid catabolism. We hypothesize that arginine acquisition is critical for <i>S. aureus</i> pathogenesis; therefore, identifying these transporters is essential for the development of novel therapeutic strategies.