Advisor: Dr. Harry Mobley
Reviewers: Drs. C. Chang & E. Martens
Bacteremia is a systemic infection associated with severe clinical outcomes that is often caused by Gram-negative facultative anaerobes. This group of bacteria have broad metabolic capabilities, and understanding regulation of these pathways in the context of the mammalian bloodstream is essential. Using global genetic screens and targeted mutational analysis, we identified the arcA metabolic regulator gene as promoting fitness of Klebsiella pneumoniae, Citrobacter freundii, and Serratia marcescens in a murine bacteremia model. ArcAB is a two-component regulatory system that serves chiefly as a repressor of aerobic respiration by responding to changes in oxygen consumption. The goal of this work is to understand why ArcAB is active during bacteremia and how repression of aerobic metabolic pathways aids in survival within the host environment. Our working model suggests that ArcAB is responsive to host conditions in which bacteria experience lower levels of oxygen and nutrient limitation impacting the cell’s ability to perform aerobic respiration. We propose ArcAB is also important in response to the host immune system. Repression of aerobic respiration by ArcAB may be advantageous in this context where bacterial cells need to reduce endogenous reactive oxygen species production and counter cellular damage affecting key metabolic machinery. Future work will focus on establishing the ArcA regulon for these species in the host environment and examining how regulation by ArcA impacts dissemination during infection.