Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans.
Phosphatidylserine (PS) synthase (Cho1p) and the PS decarboxylase enzymes (Psd1p and Psd2p), which synthesize PS and phosphatidylethanolamine (PE), respectively, are crucial for Candida albicans virulence. Mutations that disrupt these enzymes compromise virulence. These enzymes are part of the cytidine diphosphate-diacylglycerol pathway (i.e. de novo pathway) for phospholipid synthesis. Understanding how losses of PS and/or PE synthesis pathways affect the phospholipidome of Candida is important for fully understanding how these enzymes impact virulence. The cho1Δ/Δ and psd1Δ/Δ psd2Δ/Δ mutations cause similar changes in levels of phosphatidic acid, phosphatidylglycerol, phosphatidylinositol and PS. However, only slight changes were seen in PE and phosphatidylcholine (PC). This finding suggests that the alternative mechanism for making PE and PC, the Kennedy pathway, can compensate for loss of the de novo synthesis pathway. Candida albicans Cho1p, the lipid biosynthetic enzyme with the most potential as a drug target, has been biochemically characterized, and analysis of its substrate specificity and kinetics reveal that these are similar to those previously published for Saccharomyces cerevisiae Cho1p.
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Chelsi D
CD
Cassilly
Department of Chemistry, University of Tennessee, Knoxville, TN 37996, USA.
Abigail T
AT
Farmer
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Anthony E
AE
Montedonico
Biomedical Sciences Research Complex, Schools of Biology and Chemistry, The North Haugh, The University St. Andrews, Fife KY16 9ST, UK.
Terry K
TK
Smith
Department of Chemistry, University of Tennessee, Knoxville, TN 37996, USA.
Shawn R
SR
Campagna
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Todd B
TB
Reynolds
D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007700:Kinetics; D010743:Phospholipids / Q000378:metabolism*; D013379:Substrate Specificity
D010743:Phospholipids; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase
Candida albicans; lipidomics: phosphatidylserine; phosphatidylcholine; phosphatidylethanolamine; phosphatidylglycerol; phosphatidylinositol