title: The GPI-modified proteins Pga59 and Pga62 of Candida albicans are required for cell wall integrity.
abstract: The fungal cell wall is essential in maintaining cellular integrity and plays key roles in the interplay between fungal pathogens and their hosts. The PGA59 and PGA62 genes encode two short and related glycosylphosphatidylinositol-anchored cell wall proteins and their expression has been previously shown to be strongly upregulated when the human pathogen Candida albicans grows as biofilms. Using GFP fusion proteins, we have shown that Pga59 and Pga62 are cell-wall-located, N- and O-glycosylated proteins. The characterization of C. albicans pga59Delta/pga59Delta, pga62Delta/pga62Delta and pga59Delta/pga59Delta pga62Delta/pga62Delta mutants suggested a minor role of these two proteins in hyphal morphogenesis and that they are not critical to biofilm formation. Importantly, the sensitivity to different cell-wall-perturbing agents was altered in these mutants. In particular, simultaneous inactivation of PGA59 and PGA62 resulted in high sensitivity to Calcofluor white, Congo red and nikkomicin Z and in resistance to caspofungin. Furthermore, cell wall composition and observation by transmission electron microscopy indicated an altered cell wall structure in the mutant strains. Collectively, these data suggest that the cell wall proteins Pga59 and Pga62 contribute to cell wall stability and structure.
authors.affiliation: Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, INRA USC2019, Paris, France.
authors.forename: Emilia
authors.initials: E
authors.lastname: Moreno-Ruiz
authors.affiliation: Sezione di Microbiologia generale ed Applicat, DISAABA, Sassari, Italy.|Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, INRA USC2019, Paris, France.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ortu
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Piet W J
authors.initials: PWJ
authors.lastname: de Groot
authors.affiliation: Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, INRA USC2019, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Cottier
authors.affiliation: Plate-forme de Microscopie Ultrastructurale, Institut Pasteur, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Loussert
authors.affiliation: Plate-forme de Microscopie Ultrastructurale, Institut Pasteur, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prévost
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: de Koster
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frans M
authors.initials: FM
authors.lastname: Klis
authors.affiliation: Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, INRA USC2019, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Goyard
authors.affiliation: Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, INRA USC2019, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: d'Enfert
mesh_terms: D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002473:Cell Wall / Q000378:metabolism* / Q000648:ultrastructure; D005656:Fungal Proteins / Q000502:physiology*; D015870:Gene Expression; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013194:Staining and Labeling
chemical_list: D000617:Aminoglycosides; D000935:Antifungal Agents; D005656:Fungal Proteins; D017261:Glycosylphosphatidylinositols; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C011952:nikkomycin