ArticlePLoS pathogens2018
The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.
- Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.Nature communications · 2024Pooled it
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- Cryptococcal Infection Across Disease Stages: Host-Pathogen Interactions, Tissue Niches, and Translational Priorities.Pathogens (Basel, Switzerland) · 2026Review
- A role for aquaporin (Aqp1) in the control of Cryptococcus neoformans cell morphology.The Journal of biological chemistry · 2026Article
- An Organoselenium Compound Induces Death inACS omega · 2026Article
- Distinct STRIPAK subunits drive conserved and subunit-specific signaling programs inbioRxiv : the preprint server for biology · 2026Article
- Neofunctionalization of H1 linker histones drives divergent gene expression and histone methylation in Cryptococcus neoformans.Communications biology · 2026Article
- Meiosis-specific genes play roles in ploidy reduction inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ricin B lectin-like proteins mediate thermotolerance, cell wall integrity, and fungal virulence inCell surface (Amsterdam, Netherlands) · 2026Article
- Phenotypic and Molecular Characterization of Naganishia uzbekistanensis: Diagnostic Challenges and Antifungal Resistance Profile.Journal of clinical laboratory analysis · 2026Article
- 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
- Organ-specific immune responses are strain-dependent in a mouse model ofMicrobiology spectrum · 2026Article
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- The structural language of fungal cell wall sugars in WHO priority fungi: the determinant of pathogenicity and the gateway to new therapies.Frontiers in immunology · 2026Review
- The Vacuolar Protein 8 (Vac8) Homolog inJournal of fungi (Basel, Switzerland) · 2025Article
- The protein phosphatase 2C domain contributes to the pathobiological function of adenylyl cyclase inbioRxiv : the preprint server for biology · 2025Article
- Pathogenicity and virulence of Cryptococcus neoformans from an environmental perspective.Virulence · 2025Review
- Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure. Despite the important role these cells play in pathogenesis, understanding the environmental stimuli that drive the morphological transition, and the molecular mechanisms underlying their unique biology, has been hampered by the lack of a reproducible in vitro induction system. Here we demonstrate reproducible in vitro Titan cell induction in response to environmental stimuli consistent with the host lung. In vitro Titan cells exhibit all the properties of in vivo generated Titan cells, the current gold standard, including altered capsule, cell wall, size, high mother cell ploidy, and aneuploid progeny. We identify the bacterial peptidoglycan subunit Muramyl Dipeptide as a serum compound associated with shift in cell size and ploidy, and demonstrate the capacity of bronchial lavage fluid and bacterial co-culture to induce Titanisation. Additionally, we demonstrate the capacity of our assay to identify established (cAMP/PKA) and previously undescribed (USV101) regulators of Titanisation in vitro. Finally, we investigate the Titanisation capacity of clinical isolates and their impact on disease outcome. Together, these findings provide new insight into the environmental stimuli and molecular mechanisms underlying the yeast-to-Titan transition and establish an essential in vitro model for the future characterization of this important morphotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.