Antibiotic-induced alterations in the gut ecosystem increases the susceptibility to Candida albicans, yet the mechanisms involved remains poorly understood. Here we show that mice treated with the broad-spectrum antibiotic cefoperazone promoted the growth, morphogenesis and gastrointestinal (GI) colonization of C. albicans. Using metabolomics, we revealed that the cecal metabolic environment of the mice treated with cefoperazone showed a significant alteration in intestinal metabolites. Levels of carbohydrates, sugar alcohols and primary bile acids increased, whereas carboxylic acids and secondary bile acids decreased in antibiotic treated mice susceptible to C. albicans. Furthermore, using in-vitro assays, we confirmed that carbohydrates, sugar alcohols and primary bile acids promote, whereas carboxylic acids and secondary bile acids inhibit the growth and morphogenesis of C. albicans. In addition, in this study we report changes in the levels of gut metabolites correlated with shifts in the gut microbiota. Taken together, our in-vivo and in-vitro results indicate that cefoperazone-induced metabolome and microbiome alterations favor the growth and morphogenesis of C. albicans, and potentially play an important role in the GI colonization of C. albicans.

Candida albicans is a multimorphic commensal organism and opportunistic fungal pathogen in humans. A morphological switch between unicellular budding yeast and multicellular filamentous hyphal growth forms plays a vital role in the virulence of C. albicans, and this transition is regulated in response to a range of environmental cues that are encountered in distinct host niches. Many unique transcription factors contribute to the transcriptional regulatory network that integrates these distinct environmental cues and determines which phenotypic state will be expressed. These hyphal morphogenesis regulators have been extensively investigated, and represent an increasingly important focus of study, due to their central role in controlling a key C. albicans virulence attribute. This review provides a succinct summary of the transcriptional regulatory factors and environmental signals that control hyphal morphogenesis in C. albicans.

The synthesized cage-like compounds has been investigated for their antifungal activity against Candida and Cryptococcus species.