Overcoming Candida biofilm resistance: targeting persister cells with probiotic-derived metabolites

<i>Candida</i> biofilms pose a significant complication in clinical settings due to antifungal drug tolerance and the presence of persister cells. Biofilm-mediated resistance is influenced by several associated factors, including the high density and extracellular matrix characteristics of the biofilm, metabolic downregulation, efflux pump activity, and stress-response signaling pathways, which ultimately diminish drug permeability and effectiveness. Within biofilms, persister cells form a small subpopulation of cells with unique phenotypic traits that enable them to survive lethal antifungal exposure and promote the recurrence of infection. Failure of antifungal treatments in eliminating biofilm and their resilient communities suggests a need for new, adjunct treatment options Recent findings have highlighted the therapeutic potential of probiotic-derived metabolites for inhibiting certain aspects of biofilm behavior and survival. These postbiotic compounds could offer a multi-faceted, low-toxicity treatment approach that may be used as an adjunct with existing antifungal therapies. Future investigations incorporating mechanistic studies, biofilm models, and drug product development for metabolite formulations could lead to a new treatment strategy for persistent <i>Candida</i> infections.