# Molecular mechanisms of Candida albicans gut colonization

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $654,333

## Abstract

Project Summary
Candida albicans is a eukaryotic component of mammalian gut microbiota, where it exists in a
commensal state, both benefitting from and acting upon the host environment without causing
symptoms. C. albicans is also the most common cause of fungal infectious disease, which occurs upon
overgrowth and escape to ectopic sites. Existing research on commensalism has largely ignored
eukaryotes and is devoid of mechanistic detail. It is unknown how pathobiont commensals establish
their niches, or what determines the transition from commensal growth to pathogenesis. As such, tools
for the timely diagnosis and treatment of serious fungal infections are lacking. Our laboratory has taken
unbiased genetic and hypothesis-directed approaches to identify fungal regulators of gut colonization.
Using a library of >700 barcoded homozygous null mutants that we created, we identified 14 fungal
transcription factors (TFs) that determine C. albicans fitness in a mouse model of gut colonization. We
hypothesize that complex signals in local gut niches lead to TF activation, and activated TFs modulate
the expression of the fungal effectors that directly foster commensalism. Recently, we implemented a
C. albicans -Seq (CCS), which uses
transposase-transcription factor fusion proteins to permanently mark genomic sites of transcription
factor binding by transposon integration. Pairing CCS with transcriptomic analysis of mutants affecting
three TFs (Efg1, Wor1, and Czf1), we captured the in-host activity of these regulators during active gut
colonization. We then mined these datasets to predict and validate the first two commensal effector
proteins to be described in this species, determining that the GPI-anchored cell wall chitinase Cht2
promotes commensal fitness, and that the secreted aspartyl protease Sap6 inhibits commensal fitness.
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C. albicans commensal effectors; and (2) use host transcriptional responses to WT and mutant C.
albicans lacking specific effector genes to capture the impact of fungal colonization on specific host cell
types and to generate testable hypotheses for effector function.

## Key facts

- **NIH application ID:** 10979968
- **Project number:** 1R01AI179767-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SUZANNE M NOBLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $654,333
- **Award type:** 1
- **Project period:** 2024-05-10 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979968

## Citation

> US National Institutes of Health, RePORTER application 10979968, Molecular mechanisms of Candida albicans gut colonization (1R01AI179767-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10979968. Licensed CC0.

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