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dc.contributor.authorGarcia-Rodas, Rocio 
dc.contributor.authorLabbaoui, Hayet
dc.contributor.authorOrange, François
dc.contributor.authorSolis, Norma
dc.contributor.authorZaragoza, Oscar 
dc.contributor.authorFiller, Scott G
dc.contributor.authorBassilana, Martine
dc.contributor.authorArkowitz, Robert A
dc.date.accessioned2022-05-23T10:05:15Z
dc.date.available2022-05-23T10:05:15Z
dc.date.issued2022-02-15
dc.identifier.citationmBio. 2022 Feb 15;13(1):e0387321.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/14450
dc.description.abstractPhosphatidylinositol phosphates are key phospholipids with a range of regulatory roles, including membrane trafficking and cell polarity. Phosphatidylinositol-4-phosphate [PI(4)P] at the Golgi apparatus is required for the budding-to-filamentous-growth transition in the human-pathogenic fungus Candida albicans; however, the role of plasma membrane PI(4)P is unclear. We have investigated the importance of this phospholipid in C. albicans growth, stress response, and virulence by generating mutant strains with decreased levels of plasma membrane PI(4)P, via deletion of components of the PI-4-kinase complex, i.e., Efr3, Ypp1, and Stt4. The amounts of plasma membrane PI(4)P in the efr3Δ/Δ and ypp1Δ/Δ mutants were ∼60% and ∼40%, respectively, of that in the wild-type strain, whereas it was nearly undetectable in the stt4Δ/Δ mutant. All three mutants had reduced plas7ma membrane phosphatidylserine (PS). Although these mutants had normal yeast-phase growth, they were defective in filamentous growth, exhibited defects in cell wall integrity, and had an increased exposure of cell wall β(1,3)-glucan, yet they induced a range of hyphal-specific genes. In a mouse model of hematogenously disseminated candidiasis, fungal plasma membrane PI(4)P levels directly correlated with virulence; the efr3Δ/Δ mutant had wild-type virulence, the ypp1Δ/Δ mutant had attenuated virulence, and the stt4Δ/Δ mutant caused no lethality. In the mouse model of oropharyngeal candidiasis, only the ypp1Δ/Δ mutant had reduced virulence, indicating that plasma membrane PI(4)P is less important for proliferation in the oropharynx. Collectively, these results demonstrate that plasma membrane PI(4)P levels play a central role in filamentation, cell wall integrity, and virulence in C. albicans. Importance: While the PI-4-kinases Pik1 and Stt4 both produce PI(4)P, the former generates PI(4)P at the Golgi apparatus and the latter at the plasma membrane, and these two pools are functionally distinct. To address the importance of plasma membrane PI(4)P in Candida albicans, we generated deletion mutants of the three putative plasma membrane PI-4-kinase complex components and quantified the levels of plasma membrane PI(4)P in each of these strains. Our work reveals that this phosphatidylinositol phosphate is specifically critical for the yeast-to-hyphal transition, cell wall integrity, and virulence in a mouse systemic infection model. The significance of this work is in identifying a plasma membrane phospholipid that has an infection-specific role, which is attributed to the loss of plasma membrane PI(4)P resulting in β(1,3)-glucan unmasking.es_ES
dc.description.sponsorshipThis work was supported by the CNRS, INSERM, Université Côte d’Azur, and ANR (ANR-11-LABX-0028-01, ANR-16-CE13-0010-01, and ANR-19-CE13-0004-01) grants, by grant R01DE026600 from the U.S. NIH, and grant SAF2017-86192 from the Spanish Ministry for Science and Innovation. R.G.-R. is a Prestige and Marie Curie Postdoctoral Fellow (funded in part by a PCOFUND- GA-2013-609102 coordinated by Campus France).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Microbiology (ASM) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCandida albicanses_ES
dc.subjectCell walles_ES
dc.subjectFilamentous growthes_ES
dc.subjectOpportunistic fungies_ES
dc.subjectPhosphatidylinositol phosphateses_ES
dc.subjectPhospholipidses_ES
dc.subjectVirulencees_ES
dc.titlePlasma Membrane Phosphatidylinositol-4-Phosphate Is Not Necessary for Candida albicans Viability yet Is Key for Cell Wall Integrity and Systemic Infectiones_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID35164565es_ES
dc.format.volume13es_ES
dc.format.number1es_ES
dc.format.pagee0387321es_ES
dc.identifier.doi10.1128/mbio.03873-21es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) es_ES
dc.contributor.funderUniversité Côte d Azur (Francia) es_ES
dc.contributor.funderAgence Nationale de la Recherche (Francia) es_ES
dc.contributor.funderNational Institutes of Health (Estados Unidos) es_ES
dc.contributor.funderInstitut Curie es_ES
dc.contributor.funderInstitut National de la Santé et de la Recherche Médicale (Francia) es_ES
dc.contributor.funderFrench National Centre for Scientific Research (Francia) es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2150-7511es_ES
dc.relation.publisherversionhttps://doi.org/10.1128/mbio.03873-21es_ES
dc.identifier.journalMBioes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2017-86192es_ES


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