Language

English

Publication Date

9-2-2025

Journal

Microbiology Spectrum

DOI

10.1128/spectrum.00567-25

PMID

40736264

PMCID

PMC12403622

PubMedCentral® Full Text Version

Post-print

Abstract

The ubiquitous fungal pathogen Candida albicans 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 C. albicans to colonize the mouse GI tract using a representative clinical strain, CLCA10. After a single gavage challenge (5 × 106 CFU C. albicans), specific pathogen-free (SPF) mice remained colonized with C. albicans strain CLCA10, but not other Candida 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, C. albicans 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 C. albicans strains were unable to robustly colonize, strain SC5314 also colonized the mouse gut despite having enhanced pathogenicity. C. albicans 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 C. albicans gut colonization in the mouse is critically dependent on fungal hyphal factors, the targeting of which could enhance strategies to reduce C. albicans gut colonization and the intractable threat to human health it represents.IMPORTANCECandida albicans is an important human fungal pathogen and a ubiquitous colonizer of the gastrointestinal (GI) tract. However, it is not understood how C. albicans persists within the GI tract and from which it may disperse to cause disease. Here, we demonstrated that multiple strains of C. albicans, 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 C. albicans that are known to be involved in fungal virulence and unrelated to experimental conditions. Overall, this work identifies mechanisms by which C. albicans persists in the GI tract, enhancing our knowledge of host-fungal interactions during commensal colonization and potentially how to reduce such colonization.

Keywords

Animals, Candida albicans, Mice, Gastrointestinal Tract, Fungal Proteins, Candidiasis, Gastrointestinal Microbiome, Female, Specific Pathogen-Free Organisms, Symbiosis, Candida albicans, intestinal colonization, virulence factors

Published Open-Access

yes

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