ArticleBMC microbiology2015
Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A.
Article in BMC microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Article
- A conserved enzymatic toolkit targeting host cell metabolism is associated with Cryptococcus neoformans intracellular survival in protozoal and mammalian phagocytic cells.PLoS pathogens · 2025Article
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- All-stage targeted therapy for invasive cryptococcosis through interaction between the secretory protein Cig1 and hemin.Asian journal of pharmaceutical sciences · 2025Article
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- Insights from Mass Spectrometry-Based Proteomics onJournal of fungi (Basel, Switzerland) · 2025Review
- Elements of dissemination in cryptococcosis.mBio · 2024Review
- Will the Real Immunogens Please Stand Up: Exploiting the Immunogenic Potential of Cryptococcal Cell Antigens in Fungal Vaccine Development.Journal of fungi (Basel, Switzerland) · 2024Review
- Secretome analysis and virulence assessment inJournal of oral microbiology · 2024Article
- Resolving the Temporal Splenic Proteome during Fungal Infection for Discovery of Putative Dual Perspective Biomarker Signatures.Journal of the American Society for Mass Spectrometry · 2023Article
- Autophagy of Candida albicans cells after the action of earthworm Venetin-1 nanoparticle with protease inhibitor activity.Scientific reports · 2023Article
- The ER Protein Translocation Channel Subunit Sbh1 Controls Virulence of Cryptococcus neoformans.mBio · 2023Article
- Genomic and proteomic analysis of Tausonia pullulans reveals a key role for a GH15 glucoamylase in starch hydrolysis.Applied microbiology and biotechnology · 2022Article
- Secretome Profiling by Proteogenomic Analysis Shows Species-Specific, Temperature-Dependent, and Putative Virulence Proteins ofJournal of fungi (Basel, Switzerland) · 2022Article
- Article
- Article
- From Naturally-Sourced Protease Inhibitors to New Treatments for Fungal Infections.Journal of fungi (Basel, Switzerland) · 2021Review
- Proteomics ofInternational journal of molecular sciences · 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
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pathogenic yeast Cryptococcus neoformans causes life-threatening meningoencephalitis in individuals suffering from HIV/AIDS. The cyclic-AMP/protein kinase A (PKA) signal transduction pathway regulates the production of extracellular virulence factors in C. neoformans, but the influence of the pathway on the secretome has not been investigated. In this study, we performed quantitative proteomics using galactose-inducible and glucose-repressible expression of the PKA1 gene encoding the catalytic subunit of PKA to identify regulated proteins in the secretome.
methodsThe proteins in the supernatants of cultures of C. neoformans were precipitated and identified using liquid chromatography-coupled tandem mass spectrometry. We also employed multiple reaction monitoring in a targeted approach to identify fungal proteins in samples from macrophages after phagocytosis of C. neoformans cells, as well as from the blood and bronchoalveolar fluid of infected mice.
resultsWe identified 61 secreted proteins and found that changes in PKA1 expression influenced the extracellular abundance of five proteins, including the Cig1 and Aph1 proteins with known roles in virulence. We also observed a change in the secretome profile upon induction of Pka1 from proteins primarily involved in catabolic and metabolic processes to an expanded set that included proteins for translational regulation and the response to stress. We further characterized the secretome data using enrichment analysis and by predicting conventional versus non-conventional secretion. Targeted proteomics of the Pka1-regulated proteins allowed us to identify the secreted proteins in lysates of phagocytic cells containing C. neoformans, and in samples from infected mice. This analysis also revealed that modulation of PKA1 expression influences the intracellular survival of cryptococcal cells upon phagocytosis.
conclusionsOverall, we found that the cAMP/PKA pathway regulates specific components of the secretome including proteins that affect the virulence of C. neoformans. The detection of secreted cryptococcal proteins from infected phagocytic cells and tissue samples suggests their potential utility as biomarkers of infection. The proteomics data are available via ProteomeXchange with identifiers PXD002731 and PASS00736.
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