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Updated: May 3, 2026

Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans
Published on: March 19, 2015
The link between morphotype transition and virulence in Cryptococcus neoformans
Linqi Wang1, Bing Zhai, Xiaorong Lin
1Department of Biology, Texas A&M University, College Station, Texas, United States of America.
Abstract:
Cryptococcus neoformans is a ubiquitous human fungal pathogen. This pathogen can undergo morphotype transition between the yeast and the filamentous form and such morphological transition has been implicated in virulence for decades. Morphotype transition is typically observed during mating, which is governed by pheromone signaling. Paradoxically, components specific to the pheromone signaling pathways play no or minimal direct roles in virulence. Thus, the link between morphotype transition and virulence and the underlying molecular mechanism remain elusive. Here, we demonstrate that filamentation can occur independent of pheromone signaling and mating, and both mating-dependent and mating-independent morphotype transition require the transcription factor Znf2. High expression of Znf2 is necessary and sufficient to initiate and maintain sex-independent filamentous growth under host-relevant conditions in vitro and during infection. Importantly, ZNF2 overexpression abolishes fungal virulence in murine models of cryptococcosis. Thus, Znf2 bridges the sex-independent morphotype transition and fungal pathogenicity. The impacts of Znf2 on morphological switch and pathogenicity are at least partly mediated through its effects on cell adhesion property. Cfl1, a Znf2 downstream factor, regulates morphogenesis, cell adhesion, biofilm formation, and virulence. Cfl1 is the first adhesin discovered in the phylum Basidiomycota of the Kingdom Fungi. Together with previous findings in other eukaryotic pathogens, our findings support a convergent evolution of plasticity in morphology and its impact on cell adhesion as a critical adaptive trait for pathogenesis.
Insights
The transcription factor Znf2 controls the switch between yeast and filamentous forms in the fungal pathogen Cryptococcus neoformans. High Znf2 levels promote filamentous growth but surprisingly reduce fungal virulence, impacting cell adhesion.
Area of Science:
- Mycology
- Pathogenesis
- Molecular Biology
Background:
- Cryptococcus neoformans is a significant human fungal pathogen.
- Morphotype transition (yeast to filamentous form) is linked to virulence but the mechanism is unclear.
- Pheromone signaling pathways govern mating-induced morphotype transition but have minimal direct role in virulence.
Purpose of the Study:
- Investigate the molecular mechanisms linking morphotype transition and virulence in C. neoformans.
- Determine the role of the transcription factor Znf2 in morphotype transition and pathogenicity.
- Identify downstream factors of Znf2 involved in virulence.
Main Methods:
- Genetic manipulation of Znf2 expression in C. neoformans.
- In vitro and in vivo studies of fungal growth, morphology, and virulence in murine models.
- Analysis of cell adhesion properties and downstream gene expression.
Main Results:
- Filamentation occurs independently of pheromone signaling and mating, requiring the transcription factor Znf2.
- High Znf2 expression induces filamentous growth under host-relevant conditions.
- Overexpression of ZNF2 significantly reduces C. neoformans virulence in a murine cryptococcosis model.
- Znf2 impacts cell adhesion, and its downstream factor Cfl1 regulates morphogenesis, adhesion, biofilm formation, and virulence.
Conclusions:
- Znf2 is a key regulator bridging sex-independent morphotype transition and fungal pathogenicity.
- Znf2-mediated changes in cell adhesion contribute to virulence.
- Cfl1 is the first identified adhesin in Basidiomycota, highlighting the role of adhesion in pathogenesis.
- Morphological plasticity and cell adhesion represent convergent evolutionary traits for pathogenesis in eukaryotic pathogens.
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