RESEARCH
Defining nutrient sulfur acquisiton strategies employed by staphylococci
During infection, Staphylococcus aureus must acquire nutrients essential for growth from host tissues. We are interested in uncovering the strategies that S. aureus employs to fulfill the nutrient sulfur requirement by targeting sulfur-containing metabolites, such as glutathione (GSH), cysteine (Cys), and thiosulfate (ThioS). To this end, we have published papers describing the GSH import system (Gis) and demonstrating the importance of Cys transporters, TcyP and TcyABC, to S. aureus pathogenesis. Ongoing investigations seek to determine the full repertoire of S. aureus GSH acquisition and catabolic enzymes as well as establishing the importance of scavenging sulfur-containing metabolites beyond fulfilling the nutrient requirement.
identifying factors that impact staphylococcus aureus aerobic respiration
Staphylococcus aureus utilizes two terminal oxidases, CydAB (Cyd) and QoxABCD (Qox), to aerobically respire. Cyd and Qox support proliferation within specific host organs. We are interested in understanding the intrinsic and extrinsic factors that affect the activity of each terminal oxidase. To this end, we discovered a new protein required for Qox activity that we named CtaM. Experiments to elucidate the function of CtaM are ongoing.
elucidating metabolic PATHWAYS THAT SUPPORT RESPIRATION-ARRESTED METABOLISM OF S. AUREUS
In response to antibiotics, S. aureus arrests respiration and proliferates as a small colony variant (SCV). SCVs ferment to generate the energy needed to grow. Fermentation produces less ATP per carbon source, resulting in reduced growth and the production of colonies of significantly reduced size. Despite the cost due to reduced metabolic activity, an advantage of the SCV phenotype is enhanced resistance to antibiotics. Consistent with this, SCVs are isolated from patients afflicted with persistent staphylococcal infection. Two of the most common SCVs isolated from this cohort of patients are heme and menaquinone (MK) biosynthesis mutants. We seek to identify the metabolic pathways that support respiration arrested growth of heme and MK biosynthesis mutants to develop therapeutic strategies that treat persistent infections.
Understanding how bacteria exchange metabolites
With collaborators at Vanderbilt University Medical Center, we discovered that genetically distinct SCVs exchange metabolites to reverse the fitness costs associated with the SCV phenotype. We are working towards understanding how metabolite exchange happens, what other species of bacteria can exchange metabolites with S. aureus, and what metabolites can be exchanged.
