Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model

The contributions of commensal fungi to human health and disease are not well understood. species such as and are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune system and interact with the gut microbiome and pathogenic microorganisms. Therefore, species could be expected to play important ecological roles in the host gastrointestinal tract. Previously, our group demonstrated that pre-colonization of mice with protected them against lethal infection (CDI). Here, we show that mice pre-colonized with succumbed to CDI more rapidly than mice that were not pre-colonized suggesting an enhancement in pathogenesis. Further, when was added to pre-formed biofilms, an increase in matrix and overall biomass was observed. These effects were also shown with clinical isolates. Interestingly, the presence of increased biofilm susceptibility to caspofungin, indicating potential effects on the fungal cell wall. Defining this intricate and intimate relationship will lead to an understanding of the role of species in the context of CDI and novel aspects of biology. IMPORTANCE Most microbiome studies have only considered the bacterial populations while ignoring other members of the microbiome such as fungi, other eukaryotic microorganisms, and viruses. Therefore, the role of fungi in human health and disease has been significantly understudied compared to their bacterial counterparts. This has generated a significant gap in knowledge that has negatively impacted disease diagnosis, understanding, and the development of therapeutics. With the development of novel technologies, we now have an understanding of mycobiome composition, but we do not understand the roles of fungi in the host. Here, we present findings showing that , an opportunistic pathogenic yeast that colonizes the mammalian gastrointestinal tract, can impact the severity and outcome of a infection (CDI) in a murine model. These findings bring attention to fungal colonizers during CDI, a bacterial infection of the gastrointestinal tract.