# Defining the Impact of Intra-Species Diversity on C. albicans Biology

> **NIH NIH R21** · BROWN UNIVERSITY · 2021 · $250,593

## Abstract

Project Summary
 The yeast Candida albicans is a prevalent cause of life-threatening systemic disease in the clinic.
This is a highly adaptive species with the ability to occupy diverse niches in the human body, either as a
benign commensal or as an opportunistic pathogen. The diploid genome consists of eight heterozygous
chromosomes that can undergo de novo mutation, loss of heterozygosity (LOH), or larger scale
rearrangements including the acquisition or loss of whole supernumerary chromosomes. These
mechanisms generate substantial variation in the population, yet there is currently limited understanding
of how these natural differences effect interactions with the host.
 This project will examine how intra-species diversity impacts both the commensal and
pathogenic properties of C. albicans. Preliminary experiments reveal that clinical isolates exhibit
extensive genotypic differences and that additional microvariation occurs during passaging in the host.
To determine how genetic diversity impacts C. albicans biology, a sequenced collection of clinical
isolates will be barcoded and analyzed in different murine infection models. We hypothesize that
different isolates will show optimal fitness in different host niches, and our studies will reveal those
isolates that are hyper- or hypo-competitive for each niche. In parallel, a collection of SC5314 isolates
will be barcoded and analyzed for phenotypic and genotypic differences. SC5314 is the standard
“laboratory” isolate of C. albicans and yet preliminary data indicates diversity between isolates obtained
from around the world. This reveals a critical need for a detailed analysis of the SC5314 collection to
determine the level of genetic variation between strains and how this is affecting phenotypic properties.
 We will also perform a focused examination of differences in commensalism between two C.
albicans isolates, SC5314 and 529L. SC5314 is unable to colonize the murine gastrointestinal tract (GI)
in the absence of antibiotics, whereas we reveal that isolate 529L stably maintains GI colonization levels
even without antibiotic supplementation. To identify genetic loci responsible for this difference, the two
strains have been crossed to one another and recombinant progeny genotyped. These progeny will be
used for quantitative trait loci (QTL) mapping to define the loci that underlie GI colonization properties
and to understand how genetic variants impact commensalism.
 Together, these experiments will use high-throughput techniques to examine how genetic
diversity in C. albicans populations impacts commensal and pathogenic interactions with the host, as well
as a directed approach to examine factors enabling colonization of the GI tract. Our experiments will
provide greater understanding of the role that genetic variation in C. albicans plays in infection outcomes,
including the identification of mechanisms that promote adaptation to specific host niches.

## Key facts

- **NIH application ID:** 10129267
- **Project number:** 5R21AI144651-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Richard John Bennett
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $250,593
- **Award type:** 5
- **Project period:** 2020-03-18 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129267

## Citation

> US National Institutes of Health, RePORTER application 10129267, Defining the Impact of Intra-Species Diversity on C. albicans Biology (5R21AI144651-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129267. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*