Phospholipid remodeling as a target for antifungal drug development against Candida albicans

Abstract

In healthy individuals, Candida yeast species are found within the mouth and gastrointestinal tract. However, these species, particularly C. albicans, are the 4th most common cause of bloodstream infections, with an estimated mortality rate upwards of 25%. Treatment often involves two classes of anti‐fungals, one of which compromises plasma membrane integrity, establishing the membrane as a target for drug development. Limiting phospholipid remodeling may thus enhance the effect of these drugs. To test our hypothesis we created a homozygous deletion strain of a putative lysophospholipid acyltransferase (LPLAT) gene in C. albicans, designated 1881. Preliminary results indicate the 1881 double deletion‐mutation strains show mild resistance to a polyene antibiotic and two azoles. C. elegans is currently being used as a host to assess the virulence of 1881 deletion strains in an assay monitoring nematode survival after C. albicans exposure. We also hypothesize that phosphodiacylglycerol acyltransferases (PDGAT) work in conjunction with LPLATs in phospholipid remodeling. A putative PDGAT gene (designated 6018) in C. albicans is a homolog to the S. cerevisiae LRO1 gene. Generating S. cerevisiae and C. albicans deletion strains of their respective PDGAT genes, and characterizing virulence and phospholipid remodeling of these strains is our goal. Office of Sponsored Research, University of Michigan – Deaborn.