# Defining pH-Sensing in Fungal Virulence

> **NIH NIH F31** · DUKE UNIVERSITY · 2020 · $37,581

## Abstract

Abstract
 A key virulence attribute of any microbial pathogen is the ability to adapt to the conditions of the infected
host. One of these host-associated conditions is neutral/alkaline extracellular pH. Fungal pathogens use the
Rim/Pal signal transduction pathway to sense and respond to host pH. Mutants in this pathway are attenuated
for survival at alkaline pH and in the infected host. The human fungal pathogen, Cryptococcus neoformans is an
important cause of opportunistic infections in immunocompromised patients. This pathogen uses the Rim
pathway to regulate cellular changes necessary for growth at alkaline pH. This pathway was first described in
the ascomycete phylum. Interestingly, C. neoformans, a basidiomycete, lacks genes encoding many of the
components of the Rim pathway, including much of the membrane pH-sensing complex. This proposal aims to
identify proteins in the C. neoformans Rim pathway that sense changes in pH and investigate how C. neoformans
and related basidiomycetes use different strategies for sensing extracellular pH compared to model ascomycete
fungi. In Aim 1, I will use an insertional mutagenesis screen to identify. They will be further prioritized based on
phylum specificity and compelling secondary structures. In Aim 2, I will pursue an interesting finding from my
genetic screen in Aim 1 – that mutants with plasma membrane composition defects are unable to grow at alkaline
pH. In this aim, I will specifically focus on membrane bilayer asymmetry as a dynamic cellular trigger of altered
extracellular pH. I will test if the C. neoformans Cdc50 flippase, and maintenance of plasma membrane
asymmetry, is required for Rim pathway activation. These results will elucidate the molecular interactions that
drive environment-sensing in a large and biologically diverse group of fungi.

## Key facts

- **NIH application ID:** 9949366
- **Project number:** 5F31AI140427-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Hannah Elizabeth Brown
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,581
- **Award type:** 5
- **Project period:** 2019-02-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949366

## Citation

> US National Institutes of Health, RePORTER application 9949366, Defining pH-Sensing in Fungal Virulence (5F31AI140427-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9949366. Licensed CC0.

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