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

نویسندگان

چکیده

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

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ژورنال

عنوان ژورنال: International Journal of Biological Macromolecules

سال: 2021

ISSN: ['1879-0003', '0141-8130']

DOI: https://doi.org/10.1016/j.ijbiomac.2020.12.224