# Elucidating the impact of fungal adhesins on intestinal homeostasis

> **NIH NIH K22** · UNIVERSITY OF COLORADO DENVER · 2022 · $162,000

## Abstract

Project Summary/Abstract
 The intestinal microbiota regulates many facets of human health, but also harbors
commensal microbes that can exacerbate disease. Fungi are excellent examples of commensal
organisms with pathogenic potential. Fungi that dominate the intestinal fungal community
include Candida species, which are well-known opportunistic fungal pathogens. Candida have
also been shown to induce inflammation within the gut that exacerbates inflammatory bowel
disease. However, Candida are common colonizers of healthy people where they rarely cause
disease. In addition, recent work has suggested that Candida colonization may even be
beneficial by inducing immune responses that protect against mucosal and disseminated
pathogens. However, the forces that constrain Candida to a commensal lifestyle are largely
unknown. Our recent study demonstrated that adaptive immune responses serve an important
role in promoting Candida commensalism. We found that intestinal IgA antibodies target and
suppress potentially pathogenic Candida effectors, called adhesins, within the gut. Candida
adhesins are notorious virulence factors that promote host tissue adherence and invasion,
though their role in shaping fungal commensalism in the gut is unknown. For Candida albicans,
we found that adhesin expression exacerbates intestinal colitis in mice. We also found that that
an adhesin-based vaccine prevents C. albicans-associated pathology. Interestingly however, we
found that adhesin expression is associated with reduced C. albicans fitness in the gut.
Together, these data suggest that Candida adhesins are important fungal effector molecules
that potentially disrupt host and fungal homeostasis in the gut. This proposal will explore the role
of fungal adhesins in shaping host immune responses and impacting intestinal colitis. It will
leverage an adhesin-based vaccine to explore how adhesin-specific immunity shapes Candida
commensalism. This proposal will also use Candida glabrata to identify novel fungal adhesins
that regulated intestinal immune responses and colitis. These studies will significantly advance
our understanding of protective mechanisms that prevent Candida commensals from becoming
pathogenic within the gut. The results of these studies will inform the development of future
vaccines aimed at restoring homeostasis with commensal fungi.

## Key facts

- **NIH application ID:** 10429262
- **Project number:** 1K22AI168388-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kyla Ost
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $162,000
- **Award type:** 1
- **Project period:** 2022-09-21 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429262

## Citation

> US National Institutes of Health, RePORTER application 10429262, Elucidating the impact of fungal adhesins on intestinal homeostasis (1K22AI168388-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10429262. Licensed CC0.

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