# Regulation of Multidrug Resistance in the Emerging Human Fungal Pathogen Candida auris

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $193,333

## Abstract

PROJECT SUMMARY/ABSTRACT
Candida auris is a rapidly emerging human fungal pathogen capable of causing both systemic and mucosal
infections in a wide variety of immunocompromised individuals, including organ transplant recipients, cancer
patients on chemotherapy and AIDS patients. C. auris has emerged on multiple continents, is responsible for
numerous hospital outbreaks and, with a high crude mortality rate (30-70%), has been classified as an “urgent”
threat to public health by the Centers for Disease Control (CDC). Many C. auris isolates are highly resistant to
multiple classes of antifungals, particularly azoles and polyenes, which is especially concerning given that only
three major drug classes are available to treat patients with candidiasis. Previous studies have shown that C.
auris antifungal resistance can be attributed to a variety of genetic point mutations (eg: mutations in ERG11,
encoding lanosterol 14α-demethylase, the target of azoles) as well as increased transcription of certain drug
efflux pumps. In contrast to genetic and transcriptional mechanisms, very little is known about translational
mechanisms that control antifungal resistance in C. auris or other human fungal pathogens. However, our
laboratory and others, have shown that 5' UTR-mediated translational efficiency mechanisms play an important
role in controlling the expression of several key transcriptional regulators of morphology, biofilm formation,
white-opaque switching and virulence in the related major human fungal pathogen Candida albicans. In
addition, RNA-seq analyses have shown that many genes involved in a variety of additional virulence
processes, including antifungal resistance, in C. albicans and other Candida species possess long 5' UTR
regions that could be involved in translational regulation. Using genome-wide ribosome profiling, we have
recently demonstrated that the C. albicans yeast-filament transition is under widespread translational control
that does not simply parallel transcriptional changes in gene expression. Several genes associated with
antifungal resistance also showed altered translational efficiency during this transition. Importantly, recent
transcriptional profiling of a multidrug resistant C. auris isolate has demonstrated that a significant number of
genes involved in protein synthesis show altered expression in response to antifungal treatment. Based on
these observations, we hypothesize that translational mechanisms play an important role in controlling
multidrug resistance in C. auris. In order to address this hypothesis, we will: 1) determine the genome-wide
translational profile of C. auris in response to treatment with fluconazole, a commonly used azole, and the
polyene drug amphotericin B, 2) identify and characterize translational mechanisms important for promoting C.
auris multidrug resistance. Ultimately, this study will provide a better understanding of global regulatory circuits
and pathways that control C. auris multidrug r...

## Key facts

- **NIH application ID:** 10317488
- **Project number:** 1R21AI164719-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** DAVID KADOSH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,333
- **Award type:** 1
- **Project period:** 2021-05-24 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317488

## Citation

> US National Institutes of Health, RePORTER application 10317488, Regulation of Multidrug Resistance in the Emerging Human Fungal Pathogen Candida auris (1R21AI164719-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10317488. Licensed CC0.

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