Phocaeicola vulgatus mpk colonization protects epithelial cells from Candida albicans infection

Abstract Candida albicans is an opportunistic pathogen residing in the gastro-intestinal tract of humans from where it can cause life-threatening systemic infection. Dysbiosis is one predisposing factor for C. albicans overgrowth, indicating that commensal bacteria limit fungal growth and convey colonization resistance. Phocaeicola vulgatus (formerly classified as Bacteroides) is an abundant gut commensal. We show that P. vulgatus can protect enterocytes in vitro from C. albicans damage. The protective effect is most pronounced if the bacteria pre-colonize host cells 6 h prior to addition of C. albicans. Colonization of the enterocytes with P. vulgatus leads to reduced adhesion of C. albicans, shorter hyphae, and increased fungal shedding, while the overall fungal burden is not reduced. The protective effect is contact-dependent but can be elicited to some degree by heat-inactivated bacterial cells. Our findings suggest that multiple mechanisms mediate the protective effect, including activation of self-defenses of the host cells to shed the pathogen, as well as a direct antagonistic interaction between the fungi and the bacteria targeting C. albicans filamentation, and thereby hyphae-associated virulence factors.