Interkingdom Interactions between Candida albicans and Oral Anaerobes in Mixed-Species Biofilms

Candida albicans is one of the most important commensal fungi in the human body. This fungus is found in physiologically distinct niches such as the mouth, skin, gastrointestinal tract, and genitourinary tract. Candida albicans is able to colonize each of these niches due to its ability to adapt to various nutritious sources and stresses throughout its lifetime. Although Candida albicans typically maintains its commensal status in healthy individuals, perturbations to the surrounding microflora by antibiotic use or immunosuppression can lead to the overgrowth of this fungus. Here, I propose the hypothesis that anaerobic bacteria inhabiting the same gastrointestinal niches as Candida albicans inhibit its growth. A two-phase biofilm screen reveals that multiple species of Veillonella, a genus of commensal anaerobes found in the mouth and small intestine, inhibits the growth of Candida albicans. Indeed, Veillonella adheres to the yeast and hyphal forms of Candida albicans, which is associated with inhibition of their growth and a loss of fungal cell viability. This inhibition also occurs in the presence or absence of Streptococcus, a mutualistic genus of Veillonella and Candida albicans. Quantitative analysis of carbohydrates using high-pressure liquid chromatography shows that the major end-products of sugar metabolism by Streptococcus and C. albicans are lactate and ethanol, respectively. Veillonella species are known to be nonsaccharolytic bacteria that utilize Streptococcus-derived lactate for growth. Veillonella grows on lactate, but not on ethanol, thus suggesting a relatively novel model in which Veillonella species select against Candida albicans to favor competition for sugar resources by its preferred metabolic partner Streptococcus. These data are the first to investigate the mechanism and possible reason for interkingdom competition between a fungus and anaerobic bacteria in mixed-species biofilms