Commensal colonization of in the mouse gastrointestinal tract is mediated via expression of candidalysin and adhesins.

The ubiquitous fungal pathogen has the potential to either asymptomatically colonize the gastrointestinal (GI) tract or become an invasive pathogen through mechanisms that remain incompletely understood. Here we explored the fungal, host, and environmental factors that influence the ability of to colonize the mouse GI tract using a representative clinical strain, CLCA10. After a single gavage challenge (5 × 10 CFU . ), specific pathogen-free (SPF) mice remained colonized with strain CLCA10 but not other species, for at least 58 days with the fungus confined largely to the gut luminal contents. Colonized mice exhibited no weight loss or other signs of active infection, and CLCA10 did not disrupt the gut microbiome. Moreover, colonization with CLCA10 was not substantially affected by the mouse commercial source or the method used to cultivate the fungus prior to gavage. Although some genetically manipulated strains were unable to robustly colonize, strain SC5314 also colonized the mouse gut despite having enhanced pathogenicity. CLCA10 gut colonization in part depended on the hypha-associated adhesins Als3 and Hwp1 and the peptide toxin candidalysin and could not be eradicated by potent antifungal therapy. Thus, this study concludes that gut colonization in the mouse is critically dependent on fungal hyphal factors, the targeting of which could enhance strategies to reduce gut colonization and the intractable threat to human health it represents.IMPORTANCE is an important human fungal pathogen and a ubiquitous colonizer of the gastrointestinal (GI) tract. However, it is not understood how persists within the GI tract and from which it may disperse to cause disease. Here, we demonstrated that multiple strains of , including the widely used SC5314 strain, robustly colonize the mouse GI tract for at least 2 months. This colonization caused no disruption to the host tissue or bacterial microbiome and was resistant to clearance by antifungal drugs. Importantly, colonization was mediated by proteins expressed by that are known to be involved in fungal virulence and unrelated to experimental conditions. Overall, this work identifies mechanisms by which persists in the GI tract, enhancing our knowledge of host-fungal interactions during commensal colonization and potentially how to reduce such colonization.