Lactoferrin perturbs lipid rafts and requires integrity of Pma1p-lipid rafts association to exert its antifungal activity against Saccharomyces cerevisiae - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue International Journal of Biological Macromolecules Année : 2021

Lactoferrin perturbs lipid rafts and requires integrity of Pma1p-lipid rafts association to exert its antifungal activity against Saccharomyces cerevisiae

Cátia Santos-Pereira
  • Fonction : Auteur
María T Andrés
  • Fonction : Auteur
Susana R Chaves
  • Fonction : Auteur
José F Fierro
  • Fonction : Auteur
Hernâni Gerós
  • Fonction : Auteur
Lígia R Rodrigues
  • Fonction : Auteur
Manuela Côrte-Real
  • Fonction : Auteur
  • PersonId : 1114474

Résumé

Lactoferrin (Lf) is a bioactive milk-derived protein with a remarkable wide-spectrum antifungal activity. To deepen our understanding of the molecular mechanisms underlying Lf cytotoxicity, the role of plasma membrane ergosterol- and sphingolipid-rich lipid rafts and their association with the proton pump Pma1p on Lf antifungal activity was explored. Pma1p was previously identified as a Lf-binding protein. Results showed that bovine Lf (bLf) perturbs sterol-rich lipid rafts distribution by inducing their intracellular accumulation. After a deep characterization of the phenotype of yeast mutant strains lacking lipid rafts-associated proteins or enzymes involved in the synthesis of ergosterol and sphingolipids, the normal composition of these membrane domains was found crucial for bLf-induced yeast cell death. Moreover, data showed that, when Pma1p-lipid rafts association is compromised in the Pma1-10 mutant and in the absence of the Pma1p-binding protein Ast1p, the bLf killing activity is impaired. Altogether, results showed that the perturbation of lipid rafts and the inhibition of both Pma1p and V-ATPase mediate the antifungal activity of bLf. Given that the combination of conventional antifungals with lipid rafts-disrupting compounds is suggested as a powerful antifungal approach, our data will help pave the way for the use of bLf alone or in combination for the treatment/eradication of clinically and agronomically relevant yeast pathogens/fungi.
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Dates et versions

hal-03395479 , version 1 (25-10-2021)

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Cátia Santos-Pereira, María T Andrés, Susana R Chaves, José F Fierro, Hernâni Gerós, et al.. Lactoferrin perturbs lipid rafts and requires integrity of Pma1p-lipid rafts association to exert its antifungal activity against Saccharomyces cerevisiae. International Journal of Biological Macromolecules, 2021, 171, pp.343 - 357. ⟨10.1016/j.ijbiomac.2020.12.224⟩. ⟨hal-03395479⟩

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