Keeping Candida commensal: how lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model

Abstract

The intestine is the primary reservoir of Candida albicans that can cause systemic infections in immunocompromised patients. In this reservoir, the fungus exists as a harmless commensal. However, antibiotic treatment can disturb the bacterial microbiota, facilitating fungal overgrowth and favoring pathogenicity. The current in vitro gut models that are used to study the pathogenesis of C. albicans investigate the state in which C. albicans behaves as a pathogen rather than as a commensal. We present a novel in vitro gut model in which the fungal pathogenicity is reduced to a minimum by increasing the biological complexity. In this model, enterocytes represent the epithelial barrier and goblet cells limit C. albicans adhesion and invasion. Significant protection against C. albicans-induced necrotic damage was achieved by the introduction of a microbiota of antagonistic lactobacilli. We demonstrated a time-, dose- and species-dependent protective effect against C. albicans-induced cytotoxicity. This required bacterial growth, which relied on the presence of host cells, but was not dependent on the competition for adhesion sites. Lactobacillus rhamnosus reduced hyphal elongation, a key virulence attribute. Furthermore, bacterial-driven shedding of hyphae from the epithelial surface, associated with apoptotic epithelial cells, was identified as a main and novel mechanism of damage protection. However, host cell apoptosis was not the driving mechanism behind shedding. Collectively, we established an in vitro gut model that can be used to experimentally dissect commensal-like interactions of C. albicans with a bacterial microbiota and the host epithelial barrier. We also discovered fungal shedding as a novel mechanism by which bacteria contribute to the protection of epithelial surfaces..

Anti-Biofilm Properties of Saccharomyces cerevisiae CNCM I-3856 and Lacticaseibacillus rhamnosus ATCC 53103 Probiotics against G. vaginalis

“…Saccharomyces cerevisiae ( S. cerevisiae ) and the lactic acid bacterium Lacticaseibacillus rhamnosus ( L. rhamnosus ) are among the most studied probiotics [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Recently, we demonstrated, for the first time, that the probiotic yeast S. cerevisiae CNCM (French National Collection of Cultures of Microorganisms) I-3856 shows a beneficial effect in resolving experimental BV in mice [ 49 ] by interference with G. vaginalis adherence to vaginal epithelial cells (ECs), displacement of G. vaginalis attached to ECs, inhibition of sialidase activity, and reduction of vaginal epithelial exfoliation.…”

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

“…Lactobacillus species and C. albicans are a well-documented example of infectious antagonism [121][122][123]. Lactobacilli are a dominant species of the microbiota of the gastrointestinal and urogenital tracts, and they actively reduce the amount of fungal microbes by producing many fungicidal compounds [121][122][123]. Other commensal bacteria such as Bacteroides thetaiotamicron or Blautia producta can antagonize C. albicans by stimulating intestinal cells to produce antimicrobial peptides [124].…”

Therapeutic Potential of the Gut Microbiota in the Management of Sepsis

“…Interestingly, in animals pre-treated with Lactobacillus rhamnosus GG, opportunistic pathogens decreased or even disappeared, while beneficial bacteria, such as Verrucomicrobiaceae, increased, promoting inhibition of gut epithelial cell apoptosis and tight junction formation. Moreover, in a novel in vitro gut model to study Candida pathogenicity, the introduction of a microbiota of antagonistic lactobacilli emerged as a significant factor for protection against C. albicans-induced necrotic damage, with a time-, dose-, and species-dependent protective effect of probiotics against C. albicans-induced cytotoxicity [24].…”