Cryptococcus flips its lid – membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
Authors:Erika Shor1, Yina Wang1, David S. Perlin1,2, and Chaoyang Xue1,2
doi: 10.15698/mic2016.08.521
Volume 3, pp. 358 to 360, published 01/08/2016.
1 Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
2 Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Keywords:
lipid flippase, Cdc50, Cryptococcus neoformans, antifungal drug resistance, virulence.
Corresponding Author(s):
Conflict of interest statement:
Authors declare there is no competing financial or other interests that might influence the matters discussed in this article.
Please cite this article as:
Erika Shor, Yina Wang, David Perlin, and Chaoyang Xue (2016). Cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence. Microbial Cell 3(8): 358-360. doi: 10.15698/mic2016.08.521
© 2016 Shor et al. 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.
Abstract:
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.