# The biology of Cryptococcus neoformans melanization

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $809,603

## Abstract

Cryptococcus neoformans (CN) is an important human fungal pathogen responsible for thousands of deaths
each year, primarily in immunosuppressed individuals. CN makes melanin, a pigment that performs a variety of
functions in the plant and animal kingdoms. In fungi, melanin reinforces cell walls, shields against ultraviolet
radiation and toxic metals, harnesses high-energy electromagnetic radiation, and contributes to virulence. In
addition to contributing to virulence, melanization reduces the susceptibility of fungal cells to antifungal agents
and can contribute to the difficulty in treating fungal infections, which are often chronic and notoriously difficult
to eradicate. Despite its importance, little is known about the structure of melanin because it is insoluble and
amorphous, making it difficult to analyze. This research program takes a multidisciplinary approach to studying
the problem of cryptococcal melanization, combining biochemical, cell biology, and spectroscopic (solid state
NMR) techniques to uncover the mechanisms of melanization and its impact on the host-microbe interaction.
The current application proposes to elucidate the vesicular pathway used to export melanin to the exterior of the
cell, investigate the role of lipids in melanin synthesis, investigate how melanin affects the interactions between
CN and macrophages, and identify small molecule inhibitors of melanogenesis. Agents that target melanin are
potentially valuable because they could be applied against a broad array of pathogenic fungi. Four related but
independent aims are proposed: Aim 1. To establish the mechanism for CN cell wall melanization; Aim 2. To
determine how neutral lipids in lipid droplets influence melanin synthesis and deposition; Aim 3. To establish
the mechanism for how melanization subverts the CN-macrophage interaction; and Aim 4. To identify CN
melanin inhibitors and establish their mechanisms of action.

## Key facts

- **NIH application ID:** 10770563
- **Project number:** 5R01AI171093-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Arturo Casadevall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $809,603
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770563

## Citation

> US National Institutes of Health, RePORTER application 10770563, The biology of Cryptococcus neoformans melanization (5R01AI171093-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10770563. Licensed CC0.

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