1. The role of glycosylphosphatidylinositol (gpi) anchored proteins in Cryptococcusneoformans
- Author
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Eveline Snelders, Frédérique Moyrand, Aude Sturny-Leclère, Frédérique Vernel-Pauillac, Stevenn Volant, Guilhem Janbon, Alexandre Alanio, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This research received no external funding., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Institut Pasteur [Paris]-Université Paris Cité (UPC)
- Subjects
Glycosylphosphatidylinositols ,Immunology ,Cell Membrane ,Cryptococcosis ,glycophosphatidylinositol (GPI)-anchored proteins ,Microbiology ,Fungal Proteins ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Cell Wall ,Cryptococcus neoformans ,Humans ,Life Science - Abstract
International audience; It is becoming increasingly obvious that glycophosphatidylinositol (GPI)-anchored proteins (GAPs) play a prominent role in fungi, a full understanding of GAPs is however lacking especially for the human opportunistic fungus Cryptococcus neoformans. Using online GPI prediction tools, GAPs were identified and subsequently a mutant library for these GAP-encoding genes was developed and a publicly available knock out (KO) mutant library was used. In total, 41 overexpression and 34 KO mutants, representing 47 unique genes, were analyzed. From the analysis of the two libraries, two main gene candidates, a mannoprotein 88 (MP88) (CNAG_00776) and an uncharacterized protein (CNAG_00137) were further investigated by constructing additional independent mutant strains. The CNAG_00776 mutant showed an impaired growth upon plasma membrane stress and significant decreased phagocytosis. The CNAG_00137 mutant showed impaired growth during cell wall stress or increased temperature as well as decreased phagocytosis compared. By performing a large genetic screen of GAPs in the genome of the human fungal pathogen C. neoformans, we identified two candidate GAP genes involved in C. neoformans/host interaction and stress response. Further research into these two genes could potentially result in new targets for antifungals, treatment strategies or vaccines to manage C. neoformans disease.
- Published
- 2022
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