A tale of two yeasts: Saccharomyces cerevisiae as a therapeutic against candidiasis

Normally a benign commensal colonizer of mucosal surfaces such as the gastrointestinal tract, Candida albicans is also one of the most common fungal pathogens of humans, responsible for both superficial as well as life-threatening invasive infections. Arguably the commonest type of infection caused by C. albicans is vulvovaginal candidiasis (VVC), as it affects 75% of women of childbearing age. And unlike many other manifestations of candidiasis, which are associated with particular immune deficiencies, VVC frequently occurs in otherwise healthy women. Symptomatic VVC can be associated with the use of (antibacterial) antibiotics. It is thought that elimination of the protective bacterial vaginal flora allows Candida overgrowth and symptomatic disease. Indeed, for diseases of normally non-sterile sites such as mucosae, the balance of the microbial community (the microbiota) has a very important impact on the outcome of a particular host-pathogen interaction, and the presence of commensal organisms can elicit “colonization resistance” against potential pathogens. In this context, the principle of preventing or treating microbial infections with other microbes, has a long history, and a number of studies suggest that such approaches can be clinically beneficial. For example, the commensal species Clostridium scindens can protect mice from Clostridium difficile infections. Because Lactobacilli species are the dominant microbiota of the healthy vagina, imbalances in these species are implicated in VVC and there is some evidence for protective effects of Lactobacillus probiotic administration. In this issue of Virulence, Pericolini and colleagues looked at the effect of Saccharomyces cerevisiae yeast administration on the course of infection in a murine model of VVC. They found that postinfection vaginal administration of live or inactivated S. cerevisiae enhanced clearance of infecting C. albicans cells. The authors used in vivo imaging of mice infected with a C. albicans strain expressing the luciferase bioluminescent protein. Using this technique, it is possible to noninvasively track, over time, the progression, and resolution of VVC in living mice. Intriguingly, they found that a single administration of live S. cerevisiae cells elicited Candida clearance at levels comparable to treatment with the commonly used antifungal drug, fluconazole. Of note, even inactivated yeast cells elicited fungal clearance, but this was not as sustained as was observed for viable Saccharomyces cells. This suggested that S. cerevisiae cells may be used therapeutically for the treatment of VVC; but how do yeast cells help to resolve VVC? C. albicans infections of mucosal surfaces rely on a complex number of interlinked fungal pathogenicity mechanisms and virulence factors centered around the fulcrum of hyphal morphogenesis. Primarily, the pathogen must adhere robustly to its host to initiate colonization, and hypha formation strengthens adhesion potential substantially due to the expression of hypha co-expressed genes which encode the adhesin proteins Als3 and Hwp1, among others. C. albicans hyphae are also essential for epithelial invasion, not only due to the penetrative nature of the extending filament, but because the hypha coexpressed adhesin Als3 also functions as an invasin, triggering fungal uptake by epithelial cells. Although this process has not yet been tested for C. albicans-vaginal cell interactions, induced endocytosis via Als3-cadherin interactions is an established mechanism of fungal invasion of both oral epithelial and endothelia cells. C. albicans also produces an array of factors which can damage host tissue at mucosal surfaces, including secreted