Arginine Biosynthesis in Staphylococcus aureus

Crucial to the success of an invasive pathogen is the ability to utilize nutrients that are readily available in the host organism. Staphylococci have multiple amino acid auxotrophies despite having the means necessary to synthesize all twenty amino acids. Arginine is one such amino acid that is essential to all S. aureus isolates. This becomes problematic to S. aureus when the host depletes arginine from the environment to mount an immune response against bacteria. Initial studies have shown that inactivation of ccpA, a repressor/activator linked to carbon catabolite repression (CCR), facilitates growth of S. aureus on media lacking arginine. Early experimentation demonstrated that a S. aureus ccpA mutant strain synthesized arginine via proline instead of the highly conserved arginine biosynthetic pathway to synthesize arginine. Based on this observation we hypothesize that S. aureus synthesizes arginine through a novel proline degradation pathway due to the large reservoir of proline available from collagen degradation. We have shown arginine biosynthesis to be essential for survival in older abscesses (20 days). Additionally, an interruption in argH, the last gene in arginine biosynthesis and shared by the glutamate and proline pathways, resulted in reduced bacterial burden after 20 days compared to wild type S. aureus. Finally, studies of the importance of collagen degradation and praline acquisition in arginine limiting environments suggest both host factors and bacterial proteases are required for collagen degradation. Furthermore, the degraded products restore growth on media lacking praline and arginine, indicating collagen can supply these critical amino acids. These results demonstrate the importance of metabolic pathways, and specifically, arginine biosynthesis, during S. aureus growth in vivo.