# Exploiting synergistic and antagonistic interactions with antifungal drugs to improve disease treatment.

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

Project summary
 Systemic fungal infections are a primary cause of death for AIDS patients. These infections are difficult
to treat due primarily to patients’ immunocompromised state. Moreover, patients receiving treatment are
frequently taking multiple medications, creating a high potential for interactions between patients’ routine
medication and antifungal therapies. Our goal is to understand how drug-drug interactions can both improve
and complicate management of systemic fungal diseases. Drug-drug interactions can be positive (“synergistic”
– when the efficacy of the combination is greater than the sum of each drug’s activity alone), negative
(“antagonistic” – when the combined efficacy is less than the sum of each drug’s activity alone), or merely
additive. We propose to improve treatment by 1) advancing synergistic combination therapies and 2) reliable
identification of antagonistic drug interactions that decrease treatment efficacy.
 We completed a high-throughput screen for small molecules that interact with the azole class antifungal
drug fluconazole, identifying 14 synergistic partners and 8 antagonistic partners. We will advance the
synergistic pairs as potential treatments against three fungal species (Cryptococcus neoformans, Candida
albicans, and C. glabrata) by 1) quantitating improvement outcomes in vertebrate infection model of fungal
disease, 2) elucidating the molecular mechanisms underlying synergistic interactions and 3) calculating the
potential clinical impact of antagonistic interactions and determining if they are widespread within drug classes.
This work will advance potential treatments for systemic, azole-resistant fungal infections. Our analogous
studies on antagonism will facilitate prediction of these interactions to prevent harmful interactions and improve
treatments for patients with complex conditions.

## Key facts

- **NIH application ID:** 9991730
- **Project number:** 5R01AI137331-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JESSICA Conrad BROWN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2019-08-08 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991730

## Citation

> US National Institutes of Health, RePORTER application 9991730, Exploiting synergistic and antagonistic interactions with antifungal drugs to improve disease treatment. (5R01AI137331-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991730. Licensed CC0.

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