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Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence

Human fungal infections are increasing in prevalence and acquisition of antifungal drug resistance, while our antifungal drug armamentarium remains very limited, constituting a significant public health problem. Despite the fact that prominent antifungal drugs target the fungal cell membrane, very l...

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Detalles Bibliográficos
Autores principales: Shor, Erika, Wang, Yina, Perlin, David S., Xue, Chaoyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349016/
https://www.ncbi.nlm.nih.gov/pubmed/28357373
http://dx.doi.org/10.15698/mic2016.08.521
Descripción
Sumario:Human fungal infections are increasing in prevalence and acquisition of antifungal drug resistance, while our antifungal drug armamentarium remains very limited, constituting a significant public health problem. Despite the fact that prominent antifungal drugs target the fungal cell membrane, very little is known about how fungal membrane biology regulates drug-target interactions. Asymmetrical phospholipid distribution is an essential property of biological membranes, which is maintained by a group of transporters that dynamically translocate specific phospholipid groups across the membrane bilayer. Lipid flippase is the enzyme responsible for translocation of certain phospholipids, including phosphatidylserine (PS), across the plasma membrane from the exocytoplasmic to the cytoplasmic leaflet. Loss of lipid flippase leads to abnormal phospholipid distribution and impaired intracellular vesicular trafficking. The recent research article by Huang et al. reported that in pathogenic fungus Cryptococcus neoformans loss of lipid flippase activity sensitized cryptococcal cells to multiple classes of antifungal drugs, including the cell wall active echinocandins, and abolished fungal virulence in murine models. This finding demonstrates that lipid flippase may promote fungal drug resistance and virulence and indicates that this enzyme may represent a novel antifungal drug target.