ArticlePLoS pathogens2012
The link between morphotype transition and virulence in Cryptococcus neoformans.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 138 citations in OpenAlex.
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- Ovoid cell is an inducible small-sized morphotype that enhances proliferation and antifungal drug tolerance in the human fungal pathogen Cryptococcus neoformans.PLoS pathogens · 2026Article
- Systematic Profiling of Essential Fungal Transcription Factors Uncovers Ezt1 as a Central Pathobiological and Morphogenic Regulator inbioRxiv : the preprint server for biology · 2026Article
- In Silico Analysis and Expression Profiling of Adhesin-Like Flocculins in Trichosporon asahii.Mycopathologia · 2026Article
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- A conserved C2H2 zinc finger protein, Rel1, links ribosome biogenesis to sexual development and antifungal susceptibility in a ubiquitous human fungal pathogen.Applied and environmental microbiology · 2025Article
- The Zinc Finger Protein Zfp2 Regulates Cell-Cell Fusion and Virulence inJournal of fungi (Basel, Switzerland) · 2025Article
- The complex evolution and genomic dynamics of mating-type loci in Cryptococcus and Kwoniella.PLoS biology · 2025Article
- Tracing the evolution and genomic dynamics of mating-type loci inbioRxiv : the preprint server for biology · 2025Article
- The Hidden Fortress: A Comprehensive Review of Fungal Biofilms with Emphasis onJournal of fungi (Basel, Switzerland) · 2025Review
- Identification of a protective antigen reveals the trade-off between iron acquisition and antigen exposure in a global fungal pathogen.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional analysis of Saccharomyces cerevisiae FLO genes through optogenetic control.FEMS yeast research · 2025Article
- The impact of phenotypic heterogeneity on fungal pathogenicity and drug resistance.FEMS microbiology reviews · 2025Review
- Article
- Alternative isoforms and phase separation of Ref1 repress morphogenesis in Cryptococcus.Cell reports · 2024Article
- Nickel tolerance is channeled through C-4 methyl sterol oxidase Erg25 in the sterol biosynthesis pathway.PLoS genetics · 2024Article
- All hands on Dec: Treating cryptococcosis with dectin decorated liposomes loaded with antifungals.iScience · 2024Article
- Phenotypic characterization ofMicrobiology spectrum · 2024Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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.
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