Anthony R. Richardson, PhD

The Richardson Lab is primarily focused on the effects of immunometabolism on infectious disease outcomes. Immunometabolism encompasses the metabolic adaptations that a microbe must make to thrive in the face of an immune response as well as the metabolic adaptations that host cells undergo in order to mount an effective immune response. Specifically, we study immunometabolism in the context of infections caused by the Gram-positive pathogen Staphylococcus aureus. Regarding host metabolism, we are particularly interested in the roles of arginine during infection. Arginine is a semi-essential amino acid that serves two important purposes during inflammation: it is the substrate of Inducible Nitric Oxide Synthase (iNOS) for the production of nitric oxide (NO·) as well as being a substrate for Arginase-1 (Arg-1) that generates ornithine for the production of compounds known as polyamines. During a typical S. aureus skin infection, infiltrating immune cells initially express high levels of iNOS leading to robust NO· production. Eventually this inflammatory response yields to a pro-fibrotic response and a switch from iNOS to Arg-1 expression in local immune cells. These two phases of the host response exert different effects on S. aureus survival within the abscess. First, S. aureus is uniquely resistant to the effects of NO·, thus the initial inflammatory phase of the host response is ineffective at clearing the bacteria. In contrast, S. aureus is exquisitely sensitive to polyamines, which accumulate during the pro-fibrotic phase. Consequently, it is during this phase where the viable bacteria are cleared from the tissue. We are vigorously working to understand several aspects of these observations in an effort to improve treatment options against multi drug-resistant strains as well as to learn basic concepts about immunometabolism during infection.