Metabolic interplay betweenProteus mirabilisandEnterococcus faecalisfacilitates polymicrobial biofilm formation and invasive disease

Abstract

SummaryPolymicrobial biofilms play an important role in the development and pathogenesis of CAUTI.Proteus mirabilisandEnterococcus faecalisare common CAUTI pathogens that persistently co-colonize the catheterized urinary tract and form biofilms with increased biomass and antibiotic resistance. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution to CAUTI severity. Through compositional and proteomic biofilm analyses, we determined that the increase in biofilm biomass stems from an increase in the protein fraction of the polymicrobial biofilm matrix. We further observed an enrichment in proteins associated with ornithine and arginine metabolism in polymicrobial biofilms compared to single-species biofilms. We show that L-ornithine secretion byE. faecalispromotes arginine biosynthesis inP. mirabilis,and that disruption of this metabolic interplay abrogates the biofilm enhancement we seein vitroand leads to significant decreases in infection severity and dissemination in a murine CAUTI model.