d-Serine Degradation by Proteus mirabilis Contributes to Fitness during Single-Species and Polymicrobial Catheter-Associated Urinary Tract Infection.

is a common cause of catheter-associated urinary tract infection (CAUTI) and secondary bacteremia, which are frequently polymicrobial. We previously utilized transposon insertion-site sequencing (Tn-Seq) to identify novel fitness factors for colonization of the catheterized urinary tract during single-species and polymicrobial infection, revealing numerous metabolic pathways that may contribute to fitness regardless of the presence of other cocolonizing organisms. One such "core" fitness factor was d-serine utilization. In this study, we generated isogenic mutants in d-serine dehydratase (), d-serine permease (), and the divergently transcribed activator of the operon () to characterize d-serine utilization in and explore the contribution of this pathway to fitness during single-species and polymicrobial infection. was capable of utilizing either d- or l-serine as a sole carbon or nitrogen source, and , , and were each specifically required for d-serine degradation. This capability was highly conserved among isolates, although not universal among uropathogens: and utilized d-serine, while and did not. d-Serine utilization did not contribute to growth in urine during a 6-h time course but significantly contributed to fitness during single-species and polymicrobial CAUTI during a 96-h time course, regardless of d-serine utilization by the coinfecting isolate. d-Serine utilization also contributed to secondary bacteremia during CAUTI as well as survival in a direct bacteremia model. Thus, we propose d-serine utilization as a core fitness factor in and a possible target for disruption of infection. Urinary tract infections are among the most common health care-associated infections worldwide, the majority of which involve a urinary catheter (CAUTI). Our recent investigation of CAUTIs in nursing home residents identified , species, and as the three most common organisms. These infections are also often polymicrobial, and we identified , species, and as being more prevalent during polymicrobial CAUTI than single-species infection. Our research therefore focuses on identifying "core" fitness factors that are highly conserved in and that contribute to infection regardless of the presence of these other organisms. In this study, we determined that the ability to degrade d-serine, the most abundant d-amino acid in urine and serum, strongly contributes to fitness within the urinary tract, even when competing for nutrients with another organism. d-Serine uptake and degradation therefore represent potential targets for disruption of infections.