812 Talk: ArcAB contributes to bacterial fitness during Gram-negative bacteremia

Seminar Details
Friday, November 13, 2020 - 12:00pm


Aric Brown
Ph.D. Candidate, Mobley Laboratory, Department of Microbiology and Immunology


Zoom Meeting:

Meeting ID: 944 6835 3155
Passcode: 340574

Advisor: Dr. Harry Mobley

Reviewers: A. Tai & C. Wobus

Metabolic flexibility is a known characteristic of opportunistic bacteria and a prerequisite for species that transition between non-pathogenic and pathogenic environments. How bacteria adjust their metabolic profile during bacteremia to reflect the amount of oxygen and nutrients available in the bloodstream is still under investigation. The facultative anaerobes Citrobacter freundii, Klebsiella pneumoniae and Serratia marcescens are understudied agents of bacteremia that must navigate this transition. Based on transposon sequencing screens and competition infection experiments, these species have significant fitness defects associated with arcA in a murine bacteremia model. The arcA gene encodes a two-component response regulator that is part of the anoxic redox control system (ArcAB). In model organisms, ArcA serves as a global transcription factor that mediates the broad metabolic shift from aerobic respiration to fermentation. The goal of this work is to characterize the role of ArcAB in modulating the bacterial response to the bloodstream environment. Under varying levels of oxygen availability, growth kinetic experiments have shown condition-specific growth defects associated with ΔarcA strains. Results of these studies suggest ArcAB may be more important during initial phases of infection, a focus of future experiments. We have found ΔarcA mutants are more susceptible in vitro to polymyxin B, an antibiotic similar to cationic antimicrobial peptides found in blood, and hydrogen peroxide, a frontline mediator of innate immunity. Our working hypothesis is ArcAB responds to damage from these exogenous stressors by repressing carbon oxidation pathways that result in damaging reactive oxygen species production endogenously. In agreement with these results, ΔarcA mutants are also more sensitive to human serum ex vivo. Through these and future studies regarding ArcAB, we aim to build comprehensive models of pathogenesis during bacteremia to inform therapies targeting multiple species.