# Aneuploidy and Acquired Antifungal Drug Resistance in Candida species

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $440,738

## Abstract

ABSTRACT
The rapid emergence of antifungal drug resistance in Candida species poses a severe antimicrobial threat
worldwide. Azole antifungals, especially fluconazole, are widely used for treating Candida infections, however,
azoles induce genome changes in diverse Candida species and acquired resistance can rapidly emerge. Despite
this, we lack a comprehensive understanding of the molecular events that drive the acquisition of azole
resistance in real time. Previously, we identified that 50% of fluconazole resistant Candida albicans clinical
isolates are aneuploid and some of these aneuploidies cause pan-azole resistance. More recently, aneuploidy-
acquired fluconazole resistance has been observed in many diverse human fungal pathogens, yet despite the
frequency of these aneuploid events, the mechanism causing them is not known. We have developed cutting-
edge multidisciplinary approaches that uniquely position us to define the rate and mechanisms of acquired azole
resistance in a rigorous and reproducible way. These approaches include controlled in vitro and in vivo evolution,
comprehensive comparative genomics and bioinformatics techniques, and extensive molecular genetic
approaches. The aims of this application take a new approach to identifying the mechanisms driving antifungal
drug resistance. In aim 1, we will determine the impact of azole stress on the rate and dynamics of acquired
azole resistance. This will simultaneously enable us to identify novel and recurrent mechanisms of azole
resistance, aneuploidy-derived resistance mechanisms, and the extent to which these mutations cause pan-
azole and multi-drug resistance. In aim 2, the frequency of segmental chromosome aneuploidies known to cause
resistance across diverse clinical isolates will be determined both in vitro and in vivo. Additionally, the impact of
repetitive DNA sequences and DNA repair proteins on the formation of segmental aneuploidies will be
determined. Our work is significant because it will identify the frequency, order and trajectory of mutations as
they arise in a population and how these mutations cause antifungal drug resistance. Together the outcomes
from these studies will identify the mechanisms that underlie how C. albicans acquires resistance and can pave
the way for developing therapeutics to reduce the significant morbidity and mortality caused by diverse antifungal
drug resistant Candida species.

## Key facts

- **NIH application ID:** 10731749
- **Project number:** 5R01AI143689-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Anna M. Selmecki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $440,738
- **Award type:** 5
- **Project period:** 2019-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10731749

## Citation

> US National Institutes of Health, RePORTER application 10731749, Aneuploidy and Acquired Antifungal Drug Resistance in Candida species (5R01AI143689-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10731749. Licensed CC0.

---

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