# Arrestin proteins mediate microbial cellular adaptation and fungal virulence

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $241,500

## Abstract

Abstract
 In order to effectively cause disease, microorganisms must continuously sense and respond to rapidly
changing environments. For microbial pathogens, these adaptive cellular processes include the ability to respond
to host-derived stresses. The robustness with which microorganisms regulate these adaptive responses largely
determines their ability to survive within the infected host.
 In the experiments outlined in this proposal, we build upon recent and converging data from our laboratory
supporting the importance of protein ubiquitination in microbial host responses. Originally defined for directing
proteins for degradation, ubiquitination is increasingly recognized as a means of precise regulation of the
localization and function of many target proteins. In the human fungal pathogen Cryptococcus neoformans, we
have identified the Rsp5 ubiquitin ligase as a key mediator of stress response and virulence. Our preliminary
experiments have begun to define the specific aspects of the pathogenic process that require Rsp5 activity,
including cell wall homeostasis and cell cycle progression. Consistent with emerging models of ubiquitination in
diverse species, our experimental results suggest that Rsp5 is directed to its protein targets by adaptor proteins,
including the arrestin protein family. Our initial in vitro and in vivo experiments indicate that the virulence-
associated phenotypes of the C. neoformans rsp5 mutant are likely a composite of individual contribution of
altered target protein function. By further defining the microbial ubiquitin ligase / adaptor / target protein axis, we
will more deeply explore the mechanisms by which stress-induced cellular responses influence fungal infections.

## Key facts

- **NIH application ID:** 10369482
- **Project number:** 1R21AI153799-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** ANDREW ALSPAUGH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $241,500
- **Award type:** 1
- **Project period:** 2022-04-21 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369482

## Citation

> US National Institutes of Health, RePORTER application 10369482, Arrestin proteins mediate microbial cellular adaptation and fungal virulence (1R21AI153799-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10369482. Licensed CC0.

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