Phospholipidome of<i>Candida</i>: Each Species of<i>Candida</i>Has Distinctive Phospholipid Molecular Species

One sentence summary: Phosphatidylserine synthase has impacts on the whole phospholipidome of the pathogenic yeast Candida albicans. Editor: Ian Dawes ABSTRACTPhosphatidylserine (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 cho1 / and psd1 / psd2 / 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.

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“…Lipid isolations were adapted from the protocol of Singh et al (2010). Cultures were grown overnight, shaking at 30…”

Section: Lipid Isolation For Mass Spectrometry Analysismentioning

confidence: 99%

Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans

Cassilly

Farmer

Montedonico

et al. 2017

FEMS Yeast Research

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“…Data acquisition and analysis was carried out as described previously by Singh et al (21,22) with minor modifications. The extracted dry lipid samples were dissolved in 1 ml chloroform (21,22). An aliquot of 2 to 8 μl of extract in chloroform was analyzed, with the exact amount depending upon the dry lipid weight of each sample.…”

Section: Electron Spray Ionization Tandem Mass Spectrometry (Esi-ms/mmentioning

confidence: 99%

“…Processing of the data, including isotope deconvolution, was similar to that described earlier (21)(22)(23). The analyzed data (in nmol) was normalized to the sample's "dry lipid weight" to produce data in the units nmol/mg dry lipid weight.…”

Section: Electron Spray Ionization Tandem Mass Spectrometry (Esi-ms/mmentioning

confidence: 99%

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Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis

Prasad¹

2012

Front Biosci

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This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol.However, CUR alone at its synergistic concentration (lower than MIC 50 ), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in PGLs composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR.Our study first time shows that CUR, for its antifungal activity, targets and down regulates Δ 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of ROS and cell death.

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“…In C. albicans , acyl chains with a total of 34 carbons predominate in phosphatidic acid (PA), a precursor in the synthetic pathway, while the abundance of 34 and 36 carbon acyl chains is similar in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) [19]. In S. cerevisiae , cellular PC, PE, phosphatidylinositol (PI) and phosphatidylserine (PS) populations contain distinctly different acyl chain compositions [20] even though a common synthetic pathway is shared.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a lysophospholipid acyltransferase involved in membrane remodeling in Candida albicans

Ayyash

Algahmi

Gillespie

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Phospholipid remodeling involves phospholipase activity to remove acyl chains and acyltransferases to replace acyl chains. We here describe the characterization of a lysophospholipid acyltransferase in the opportunistic fungal pathogen, Candida albicans. Expression of this gene, C.a. LPT1, complemented the lysophospholipid acyltransferase defect in Saccharomyces cerevisiae strains lacking the homologous LPT1 gene. In vitro, lysophospholipid acyltransferase activity in these strains showed acyl-CoA substrate specificity, as measured by apparent Vmax/Km ratios, to be linolenoyl-CoA > oleoyl-CoA > linoleoyl-CoA > stearoyl-CoA. To address the physiological importance of C.a. LPT1, homozygous deletion strains were generated. Lysophospholipid acyltransferase activity with amine containing lysophospholipids was dramatically reduced while lysophosphatidylinositol and lysophosphatidic acid esterification was not significantly lowered. However, C.a. LPT1 over-expression yielded an increased amount of lysophosphatidic acyltransferase activity, suggesting a role in de novo phospholipid synthesis. LPT1 deletion strains showed slightly slowed growth in standard liquid media but no phenotype in media containing three antifungals that target sterols. To assess the role of C.a. Lpt1 in phospholipid remodeling, an in vivo, pulse–chase assay utilizing polysorbitan palmitate and mass spectrometry was developed. Cellular phospholipid composition became atypical with the provision of palmitate and gradually returned to the typical distribution when palmitate was removed. Deletion of C.a. LPT1 showed a modest yet significant effect on remodeling under these conditions.

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Phospholipidome ofCandida: Each Species ofCandidaHas Distinctive Phospholipid Molecular Species

Cited by 44 publications

References 30 publications

Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans

Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans

Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis

Characterization of a lysophospholipid acyltransferase involved in membrane remodeling in Candida albicans

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