# Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $374,231

## Abstract

Abstract
 This competitive renewal will continue to work on understanding the population genetic structures of
Cryptococcus neoformans. With this massive genome sequencing data, we will expand it and add a functional
and/or translational focus. Importantly, the sequence data are integrated with phenotypic data, animal models
and human infection outcomes to help understand the genetic components that make it a deadly human
pathogen.Cryptococcus neoformans represents a group of encapsulated basidiomycetous yeasts that continue
to produce hundreds of thousands of cases of meningitis each year with mortality rates of 15 to over 50%
depending on the health care systems and no new antifungal agents have been discovered for its treatment in
25 years. In this proposal, we will use whole genome sequences to direct a research platform to complete two
Specific Aims that are framed in questions. Specific Aim 1 is: What are the genotypic and phenotypic
differences between clinical and environmental strains. Specific Aim 2 examines the following
question: Within clinical isolates that have already produced disease, why are some strains more
virulent or aggressive than others? The goal of this proposal is three- fold. First, to use whole genome
sequencing (WGS) and GWAS in a large number of strains linked to functional data in order to dial down into
wild-type strains and find specific genes and/or networks important to C. neoformans fitness/survival in the
mammalian host. Thus, we will identify potential weak spots in the fungus to be used for antifungal drug
targets. Second, to genetically identify “bad actor” strains producing more aggressive disease behaviors that
could be identified for the treating clinician to appreciate and thus adjust treatment regimens based on this
knowledge of the strain’s pathobiology. Finally, this study will create a substantial infrastructure addition of a
library of well-characterized wild-type strains for use by the entire cryptococcal community for future
pathobiology work.

## Key facts

- **NIH application ID:** 10199975
- **Project number:** 5R01AI093257-09
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** John R. Perfect
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $374,231
- **Award type:** 5
- **Project period:** 2011-08-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199975

## Citation

> US National Institutes of Health, RePORTER application 10199975, Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS (5R01AI093257-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10199975. Licensed CC0.

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