Differential Contribution of Hydrogen Metabolism to Fitness during Single-Species and Polymicrobial Catheterized Urinary Tract Infection.

is a common uropathogen and a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Through a genome-wide screen, we previously identified two [NiFe] hydrogenases as candidate fitness factors for CAUTI: a Hyb-type Group 1c H-uptake hydrogenase and a Hyf-type Group 4a H-producing hydrogenase. In this study, we disrupted one gene of each system ( and ) and also generated a double mutant to examine the contribution of flexible H metabolism to growth and fitness in vitro and during experimental CAUTI. Since is typically present as part of a polymicrobial community in the urinary tract, we also examined the impact of two common co-colonization partners, and , on the expression and contribution of each hydrogenase to fitness. Our data demonstrate that neither system alone is critical for growth in vitro or fitness during experimental CAUTI. However, perturbation of flexible H metabolism in the ∆∆ double mutant decreased fitness in vitro and during infection. The Hyf system alone contributed to the generation of proton motive force and swarming motility, but only during anaerobic conditions. Unexpectedly, both systems contributed to benzyl viologen reduction in TYET medium, and disruption of either system increased expression of the other. We further demonstrate that polymicrobial interactions with and alter the expression of Hyb and Hyf in vitro as well as the contribution of each system to fitness during CAUTI.