The goal of project #2 of this PPG is to investigate the hypothesis that Staphylococcus aureus must fine-tune its central metabolism for rapid adaptation to different carbon and nitrogen sources available within a given tissue microenvironment. S. aureus has the ability to colonize or cause infection in a multitude of organ systems in the human host and therefore must adapt to changing carbon and nitrogen sources within each niche. We have focused our studies on a staphylococcal abscess, which is glucose depleted, and how S. aureus persists with secondary carbon sources such as amino acids and peptides as the major carbon source. Based on our previous data, a model has been developed predicting that S. aureus cleaves specific host proteins facilitating transport of peptides through oligopeptides transporters (Opp-3). Preliminary studies document that peptide transport induces protease transcription linking these two fundamental processes. Lastly, we have documented the amino acid catabolic pathways that are critical for growth when S. aureus is growing on amino acids as the sole carbon source. The proposed aims build upon our developing model and 1) determine the function and receptor kinetics of the four S. aureus proline transporters and relevance of proline transport in mouse models of infection; 2) Investigate the relationship between peptide transport and induction of protease transcription; and 3) Interrogate the importance of pyruvate generating amino acid catabolism and subsequent acetate generation during growth in media lacking glucose.
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