ArticleInfection and immunity2014
Fbp1-mediated ubiquitin-proteasome pathway controls Cryptococcus neoformans virulence by regulating fungal intracellular growth in macrophages.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Article
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- Ubiquitin degradation of the Ribonuclease H2 subunit B Rnh2B regulates the virulence ofVirulence · 2025Article
- Insights from Mass Spectrometry-Based Proteomics onJournal of fungi (Basel, Switzerland) · 2025Review
- Deubiquitinase Ubp5 is essential for pulmonary immune evasion and hematogenous dissemination ofMycology · 2025Article
- Efficacy and Molecular Mechanisms of Nystatin AgainstFoods (Basel, Switzerland) · 2024Article
- Preclinical Models for Cryptococcosis of the CNS and Their Characterization Using In Vivo Imaging Techniques.Journal of fungi (Basel, Switzerland) · 2024Review
- Vaccine Strategies for Cryptococcus neoformans.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Dendritic Cells: Multifunctional Roles in Host Defenses toJournal of fungi (Basel, Switzerland) · 2023Review
- Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction ofJournal of fungi (Basel, Switzerland) · 2023Article
- Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023Review
- Multiple F-Box Proteins Collectively Regulate Cell Development and Pathogenesis in the Human PathogenJournal of fungi (Basel, Switzerland) · 2022Article
- Ubiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans.Nature communications · 2022Article
- Harnessing the Immune Response to Fungal Pathogens for Vaccine Development.Annual review of microbiology · 2022Review
- Macrophage Mediated Immunomodulation DuringFrontiers in cellular and infection microbiology · 2022Review
- The Vacuolar Morphogenesis Protein Vam6-Like Protein Vlp1 Is Required for Pathogenicity ofJournal of fungi (Basel, Switzerland) · 2021Article
- HOG1 has an essential role in the stress response, virulence and pathogenicity ofExperimental and therapeutic medicine · 2021Article
- Post-Translational Modifications Drive Success and Failure of Fungal-Host Interactions.Journal of fungi (Basel, Switzerland) · 2021Review
- More Than Just Cleaning: Ubiquitin-Mediated Proteolysis in Fungal Pathogenesis.Frontiers in cellular and infection microbiology · 2021Review
- Pathogen-Host Interaction Repertoire at Proteome and Posttranslational Modification Levels During Fungal Infections.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cryptococcus neoformans is a human fungal pathogen that often causes lung and brain infections in immunocompromised patients, with a high fatality rate. Our previous results showed that an F-box protein, Fbp1, is essential for Cryptococcus virulence independent of the classical virulence factors, suggesting a novel virulence control mechanism. In this study, we show that Fbp1 is part of the ubiquitin-proteasome system, and we further investigated the mechanism of Fbp1 function during infection. Time course studies revealed that the fbp1Δ mutant causes little damage in the infected lung and that the fungal burden in the lung remains at a low but persistent level throughout infection. The fbp1Δ mutant cannot disseminate to other organs following pulmonary infection in the murine inhalation model of cryptococcosis but still causes brain infection in a murine intravenous injection model, suggesting that the block of dissemination of the fbp1Δ mutant is due to its inability to leave the lung. The fbp1Δ mutant showed a defect in intracellular proliferation after phagocytosis in a Cryptococcus-macrophage interaction assay, which likely contributes to its virulence attenuation. To elucidate the molecular basis of the SCF(Fbp1) E3 ligase function, we analyzed potential Fbp1 substrates based on proteomic approaches combined with phenotypic analysis. One substrate, the inositol phosphosphingolipid-phospholipase C1 (Isc1), is required for fungal survival inside macrophage cells, which is consistent with the role of Fbp1 in regulating Cryptococcus-macrophage interaction and fungal virulence. Our results thus reveal a new determinant of fungal virulence that involves the posttranslational regulation of inositol sphingolipid biosynthesis.
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