Glycerophosphocholine Utilization by Candida albicans

Bishop, Andrew C.; Ganguly, Shantanu; Solis, Norma V.; Cooley, Benjamin M.; Jensen‐Seaman, Michael I.; Filler, Scott G.; Mitchell, Aaron P.; Patton‐Vogt, Jana

doi:10.1074/jbc.m113.505735

Cited by 24 publications

(43 citation statements)

References 60 publications

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“…data 3). Indeed, it has been shown that the ability of C. albicans to utilize external glycero-phosphocholine is important for virulence in murine systemic candidiasis29 and that RHR2 is essential for proliferation of C. albicans in the liver of intraperitoneally infected mice30.…”

Section: Resultsmentioning

confidence: 99%

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

Hebecker

Vlaic

Conrad

et al. 2016

Sci Rep

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Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.

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Section: Resultsmentioning

confidence: 99%

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

Hebecker

Vlaic

Conrad

et al. 2016

Sci Rep

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“…It should be noted that GPC is believed to only be formed via deacylation of PC, and if so, GPCAT cannot contribute to any net synthesis of PC if GPC is not provided to the cell from outside. Because plasma membrane GPC transporters are found in yeast (5, 17) and fungi (18), exogenous GPC could, however, under certain environmental conditions contribute to net synthesis of PC via GPCAT in these cells. In all cells, GPCATs would contribute to an acyl editing, whereby acyl groups from the acyl-CoA pool can be inserted into the s n -1 position of PC via LPC formation from GPC.…”

Section: Discussionmentioning

confidence: 99%

Cloning of Glycerophosphocholine Acyltransferase (GPCAT) from Fungi and Plants

Głąb

Beganovic

Anaokar

et al. 2016

Journal of Biological Chemistry

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Glycero-3-phosphocholine (GPC), the product of the complete deacylation of phosphatidylcholine (PC), was long thought to not be a substrate for reacylation. However, it was recently shown that cell-free extracts from yeast and plants could acylate GPC with acyl groups from acyl-CoA. By screening enzyme activities of extracts derived from a yeast knock-out collection, we were able to identify and clone the yeast gene (GPC1) encoding the enzyme, named glycerophosphocholine acyltransferase (GPCAT). By homology search, we also identified and cloned GPCAT genes from three plant species. All enzymes utilize acyl-CoA to acylate GPC, forming lyso-PC, and they show broad acyl specificities in both yeast and plants. In addition to acyl-CoA, GPCAT efficiently utilizes LPC and lysophosphatidylethanolamine as acyl donors in the acylation of GPC. GPCAT homologues were found in the major eukaryotic organism groups but not in prokaryotes or chordates. The enzyme forms its own protein family and does not contain any of the acyl binding or lipase motifs that are present in other studied acyltransferases and transacylases. In vivo labeling studies confirm a role for Gpc1p in PC biosynthesis in yeast. It is postulated that GPCATs contribute to the maintenance of PC homeostasis and also have specific functions in acyl editing of PC (e.g. in transferring acyl groups modified at the sn-2 position of PC to the sn-1 position of this molecule in plant cells).

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“…The secreted/periplasmic form of Plb1 is most likely responsible for the production of extracellular GroPCho. Notably, extracellular GroPCho is not a dead end metabolite but can be recycled into PC synthesis following its uptake via glycerophosphodiester transporters that have been identified in both S. cerevisiae (74) and Candida albicans (46,75).…”

Section: Discussionmentioning

confidence: 99%

Loss of Ypk1, the Yeast Homolog to the Human Serum- and Glucocorticoid-induced Protein Kinase, Accelerates Phospholipase B1-mediated Phosphatidylcholine Deacylation

Surlow

Cooley

Needham

et al. 2014

Journal of Biological Chemistry

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Background: Ypk1 is a protein kinase known to regulate sphingolipid homeostasis. Plb1 deacylates phosphatidylcholine to produce glycerophosphocholine. Results: Loss of Ypk1 or disruption of sphingolipid synthesis by other means elevates Plb1-mediated phosphatidylcholine turnover. Conclusion: Accelerated turnover of phosphatidylcholine compensates for aberrant sphingolipid synthesis. Significance: Sphingolipid synthesis is coordinated with phosphatidylcholine metabolism to maintain membrane lipid homeostasis.

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Glycerophosphocholine Utilization by Candida albicans

Cited by 24 publications

References 60 publications

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

Cloning of Glycerophosphocholine Acyltransferase (GPCAT) from Fungi and Plants

Loss of Ypk1, the Yeast Homolog to the Human Serum- and Glucocorticoid-induced Protein Kinase, Accelerates Phospholipase B1-mediated Phosphatidylcholine Deacylation

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