2026-07-23T17:42:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/144502024-09-27T22:39:09Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Garcia-Rodas, Rocio
author
Labbaoui, Hayet
author
Orange, François
author
Solis, Norma
author
Zaragoza, Oscar
author
Filler, Scott G
author
Bassilana, Martine
author
Arkowitz, Robert A
funder
Ministerio de Ciencia e Innovación (España)
funder
Université Côte d Azur (Francia)
funder
Agence Nationale de la Recherche (Francia)
funder
National Institutes of Health (Estados Unidos)
funder
Institut Curie
funder
Institut National de la Santé et de la Recherche Médicale (Francia)
funder
French National Centre for Scientific Research (Francia)
2022-05-23T10:05:15Z
2022-05-23T10:05:15Z
2022-02-15
mBio. 2022 Feb 15;13(1):e0387321.
10.1128/mbio.03873-21
2150-7511
MBio
35164565
http://hdl.handle.net/20.500.12105/14450
Phosphatidylinositol 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.
eng
Candida albicans
Cell wall
Filamentous growth
Opportunistic fungi
Phosphatidylinositol phosphates
Phospholipids
Virulence
Plasma Membrane Phosphatidylinositol-4-Phosphate Is Not Necessary for Candida albicans Viability yet Is Key for Cell Wall Integrity and Systemic Infection
journal article
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