title: Pga26 mediates filamentation and biofilm formation and is required for virulence in Candida albicans.
abstract: The Candida albicans gene PGA26 encodes a small cell wall protein and is upregulated during de novo wall synthesis in protoplasts. Disruption of PGA26 caused hypersensitivity to cell wall-perturbing compounds (Calcofluor white and Congo red) and to zymolyase, which degrades the cell wall β-1,3-glucan network. However, susceptibility to caspofungin, an inhibitor of β-1,3-glucan synthesis, was decreased. In addition, pga26Δ mutants show increased susceptibility to antifungals (fluconazol, posaconazol or amphotericin B) that target the plasma membrane and have altered sensitivities to environmental (heat, osmotic and oxidative) stresses. Except for a threefold increase in β-1,6-glucan and a slightly widened outer mannoprotein layer, the cell wall composition and structure was largely unaltered. Therefore, Pga26 is important for proper cell wall integrity, but does not seem to be directly involved in the synthesis of cell wall components. Deletion of PGA26 further leads to hyperfilamentation, increased biofilm formation and reduced virulence in a mouse model of disseminated candidiasis. We propose that deletion of PGA26 may cause an imbalance in the morphological switching ability of Candida, leading to attenuated dissemination and infection.
authors: Departamento de Microbiología y Ecología, Universidad de Valencia, Burjassot, Spain.
authors: Leslie
authors: L
authors: Laforet
authors: Inmaculada
authors: I
authors: Moreno
authors: Ruth
authors: R
authors: Sánchez-Fresneda
authors: María
authors: M
authors: Martínez-Esparza
authors: José P
authors: JP
authors: Martínez
authors: Juan-Carlos
authors: JC
authors: Argüelles
authors: Piet W J
authors: PW
authors: de Groot
authors: Eulogio
authors: E
authors: Valentín-Gomez
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D000077336:Caspofungin; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D054714:Echinocandins / Q000494:pharmacology; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D025301:Hyphae / Q000254:growth & development; D007155:Immunologic Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D055666:Lipopeptides; D051379:Mice; D023421:Models, Animal; D017384:Sequence Deletion; D013312:Stress, Physiological / Q000502:physiology; D014774:Virulence; D047071:beta-Glucans / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D017261:Glycosylphosphatidylinositols; D007155:Immunologic Factors; D055666:Lipopeptides; D047071:beta-Glucans; C064197:beta-1,6-glucan; C033363:beta-1,3-glucan; D000077336:Caspofungin