Catalase Activity is Critical for Proteus mirabilis Biofilm Development, EPS Composition, and Dissemination During Catheter-Associated Urinary Tract Infection

Abstract

AbstractProteus mirabilis is a leading uropathogen of catheter-associated urinary tract infections (CAUTIs), which are among the most common healthcare-associated infections worldwide. A key factor that contributes to P. mirabilis pathogenesis and persistence during CAUTI is the formation of catheter biofilms, which provide increased resistance to antibiotic treatment and host defense mechanisms. Another factor that is important for bacterial persistence during CAUTI is the ability to resist reactive oxygen species (ROS), such as through the action of the catalase enzyme. Potent catalase activity is one of the defining biochemical characteristics of P. mirabilis, and its single catalase gene (katA) was recently identified as a candidate fitness factor for UTI, CAUTI, and bacteremia. Here we show that disruption of katA results in increased ROS levels, increased sensitivity to peroxide, and decreased biofilm biomass. The biomass defect was due to a decrease in extracellular polymeric substances (EPS) production by the ΔkatA mutant, and specifically due to reduced carbohydrate content. Importantly, the biofilm defect resulted in decreased antibiotic resistance in vitro and a colonization defect during experimental CAUTI. The ΔkatA mutant also exhibited decreased fitness in a bacteremia model, supporting a dual role for catalase in P. mirabilis biofilm development and immune evasion.