title: Cryptococcusflips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence.
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 Huanget al.reported that in pathogenic fungusCryptococcus neoformansloss 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.
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Shor
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Yina
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA. ; Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA. ; Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Xue
keywords: Cdc50; Cryptococcus neoformans; antifungal drug resistance; lipid flippase; virulence