Calling a Truce: Enterococcus faecalis as a mediator between E. coli and C. albicans during polymicrobial CAUTIs

Polymicrobial catheter-associated urinary tract infections (CAUTIs) are a severe clinical burden. CAUTIs promote colonization by different microbes, including E. faecalis, E. coli, and C. albicans. These mixed biofilms can compromise antimicrobial efficacy and promote resistance. Despite their prevalence, the cross-kingdom dynamics driving these infections within the catheterized bladder remain poorly understood. Using established in vitro and in vivo CAUTI models, we elucidate the complex, environment-dependent interactions governing these multispecies biofilms. We demonstrate that E. coli strongly antagonizes C. albicans, by limiting iron uptake, inhibiting filamentation, and inducing cell death. Crucially, we identify E. faecalis as a protective keystone species that mitigates this antagonism. E. faecalis facilitates multispecies coexistence by acting as a spatial bridge on the urothelium, enabling E. coli and C. albicans to co-localize rather than occupy segregated niches. These mechanistic insights into polymicrobial synergy and competition provide a crucial framework for developing targeted therapeutics against recalcitrant CAUTIs.