# Candida Determinants of GI Tract Colonization

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $563,570

## Abstract

PROJECT SUMMARY
 Candida species are the primary cause of systemic fungal infections in nosocomial environments.
Several of these species are common components of the human intestinal microbiota where they have been
increasingly linked with mucosal disorders such as inflammatory bowel disease (IBD). Candida cells in the gut
are also a critical reservoir for systemic infections as they can translocate out of this niche and disseminate
throughout the body, particularly in immunocompromised individuals. There is therefore a pressing need to
understand how Candida colonizes the GI tract and to define how changes to the commensal environment
impact colonization behavior and the immune response.
 This project addresses the attributes of Candida cells that enables them to colonize the mammalian
gastrointestinal (GI) tract. Despite the importance of Candida to both gut mucosal and systemic disease, a
substantial knowledge gap exists in defining the molecular mechanisms that support colonization of the GI
tract. In the case of Candida albicans (Ca), the most prevalent cause of fungal systemic disease, previous
studies have indicated that yeast cells are optimal for gut colonization, whereas cells in the hyphal (filamentous)
state are detrimental to commensalism but critical for systemic virulence. These studies are based on antibiotic-
supplemented hosts, however, and our pilot experiments reveal the hyphal state plays an essential role in
colonization of hosts that harbor an antibiotic-naïve microbiome. Furthermore, we demonstrate that
candidalysin, a toxin secreted by hyphal Ca cells, is critical for colonization of the GI tract when bacteria are
present, indicating that this factor supports competition with the bacterial microbiota.
 To build on these observations, we will examine how Candida morphology and co-regulated genes
enable host colonization, while focusing on both Ca and the related species Candida parapsilosis (Cp). The
Aims of this Project are (1) To define the effects of Candida morphology on fungal metabolism and intestinal
fitness, (2) To determine the role of candidalysin in intestinal colonization, and (3) To use quantitative trait loci
(QTL) mapping to identify traits impacting Candida commensalism. We emphasize that these experiments will
use a wide variety of murine GI models that harbor either native bacterial populations or engineered microbial
populations to determine how interkingdom interactions influence fungal gut commensalism.
 Together, these experiments will build on exciting preliminary experiments that overturn the prevailing
paradigm that yeast-locked Candida cells are optimal for colonization, and that the hyphal-specific toxin
candidalysin is a key gut colonization factor in addition to an established virulence factor. Given the importance
of gut colonization to fungal-host interactions and systemic disease, these experiments will provide critical new
insights into understanding how Candida species operate as human pa...

## Key facts

- **NIH application ID:** 10763696
- **Project number:** 1P01AI179406-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** TOBIAS M HOHL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $563,570
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763696

## Citation

> US National Institutes of Health, RePORTER application 10763696, Candida Determinants of GI Tract Colonization (1P01AI179406-01). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10763696. Licensed CC0.

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