# Investigating a signaling molecule that cooperates with quorum sensing to induce biofilm formation in C. neoformans

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2023 · $226,500

## Abstract

ABSTRACT
The objectives of this exploratory R21 proposal are to identify and characterize an intercellular communication
signal that induces biofilm formation in cooperation with quorum sensing in the human fungal pathogen
Cryptococcus neoformans. C. neoformans is a basidiomycetous fungus that causes cryptococcal
meningoencephalitis (CME), one of the most fatal and common opportunistic infections affecting people with
HIV/AIDS. Like many other infectious microbes, C. neoformans forms biofilm-like structures known as
cryptococcoma in vivo. However, we know very little about the structural requirements for biofilms or their
genetic regulation in this fungal pathogen, partly because Cryptococcus forms biofilms poorly under laboratory
conditions, and partly because this basidiomycete does not carry homologues of any known biofilm-relevant
proteins established in ascomycetes like Saccharomyces and Candida species.
Here we found that disruption of a transcription repressor Ssn6 in a mating-type a strain, but not in the
congenic mating-type α strain, leads to robust biofilm formation in C. neoformans, which provides an entry
point for us to investigate genetic regulation of biofilm formation in this fungus. Interestingly, ssn6a biofilm
colonies induce the nearby ssn6α colonies to also form biofilms and this process is independent of the mating
pheromone. We discovered that the intercellular communication system which activates biofilm formation
requires the quorum-sensing molecule Qsp1 and an unknown peptide-based signaling molecule. Here we
propose to (1) identify the secreted biofilm signaling molecule and (2) elucidate the pathway involved in biofilm
formation activated by this signaling molecule. The proposed work is expected to yield insights into this layered
communication system that regulates such complex community behaviors in a clinically important fungal
pathogen. We also expect to identify novel biofilm structural proteins like adhesins in Cryptococcus in this
process, which will fill the critical gap in our knowledge about biofilm formation and regulation in
basidiomycetes. The findings from this exploratory research will also provide a foundation for future
investigation of the impact of biofilm regulation on cryptococcal pathogenesis.

## Key facts

- **NIH application ID:** 10550504
- **Project number:** 1R21AI172787-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Xiaorong Lin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $226,500
- **Award type:** 1
- **Project period:** 2022-11-25 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10550504

## Citation

> US National Institutes of Health, RePORTER application 10550504, Investigating a signaling molecule that cooperates with quorum sensing to induce biofilm formation in C. neoformans (1R21AI172787-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10550504. Licensed CC0.

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