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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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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
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author Shor, Erika
Wang, Yina
Perlin, David S.
Xue, Chaoyang
author_facet Shor, Erika
Wang, Yina
Perlin, David S.
Xue, Chaoyang
author_sort Shor, Erika
collection PubMed
description 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.
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spelling pubmed-53490162017-03-29 Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence Shor, Erika Wang, Yina Perlin, David S. Xue, Chaoyang Microb Cell Microbiology 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. Shared Science Publishers OG 2016-08-01 /pmc/articles/PMC5349016/ /pubmed/28357373 http://dx.doi.org/10.15698/mic2016.08.521 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Microbiology
Shor, Erika
Wang, Yina
Perlin, David S.
Xue, Chaoyang
Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
title Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
title_full Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
title_fullStr Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
title_full_unstemmed Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
title_short Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
title_sort cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
topic Microbiology
url 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
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