# Development and application of auxin-inducible degradation in Candida pathogens

> **NIH NIH R21** · PURDUE UNIVERSITY · 2024 · $192,017

## Abstract

PROJECT SUMMARY
Opportunistic fungal infection of immune-compromised individuals is an escalating world health problem,
recently highlighted in a report from the World Health Organization. Lethal outbreaks of multi drug-resistant
Candida auris in hospitals and the rise of drug resistance in normally benign commensal fungal species like
Candida glabrata highlight the severity of the problem. Even severe COVID-19 cases facilitate secondary
infection by fungal pathogens like Aspergillus and Candida that can be lethal. Current treatment options for
fungal infections are limited to a few antifungal drug classes that are becoming increasingly ineffective. There
is a pressing need for new molecular targets for antifungal development to deal with drug-resistant pathogens.
Our central objective is to establish auxin-inducible degradation (AID) technology in Candida pathogens to
enable functional studies of virulence and drug resistance factors and as a tool to facilitate antifungal target
validation in the early stages of antifungal drug discovery. AID provides rapid and specific depletion of target
proteins of interest and has key advantages over other common methods for protein functional
characterization. In Aim 1 we will engineer molecular biology reagents and strains, and establish protocols, to
validate and implement a modified AID system in C. albicans, C. glabrata, and C. auris. Our novel system
should be applicable in any strain, including clinical isolates, of Candida pathogen species. Validation
experiments will use novel virulence and drug resistance factors identified in our labs. In Aim 2 we will combine
AID technology in Candida species with two common animal infection models, Galleria mellonella (waxworm)
larvae and immunosuppressed mice, to create systems for early target validation and in vivo simulation of drug
effects on pathogenesis. These systems will also be applied to our novel candidate antifungal targets. AID is a
powerful functional genomics tool that will enable new research opportunities in fungal pathogens. Reagents
and protocols established during the project will be made available to the research community, and the work
will establish a blueprint for expanding AID use to other diverse fungal pathogens. Overall, this technological
platform will address the pressing need for identification and validation of viable new targets for antifungal
therapeutic development.

## Key facts

- **NIH application ID:** 10913591
- **Project number:** 5R21AI174123-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Mark C Hall
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $192,017
- **Award type:** 5
- **Project period:** 2023-08-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913591

## Citation

> US National Institutes of Health, RePORTER application 10913591, Development and application of auxin-inducible degradation in Candida pathogens (5R21AI174123-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10913591. Licensed CC0.

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