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Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans

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Date
03/2017
Author
Cassilly, Chelsi D.
Farmer, Abigail T.
Montedonico, Anthony E.
Smith, Terry K.
Campagna, Shawn R.
Reynolds, Todd B.
Keywords
Lipidomics
Phosphatidylserine
Phosphatidylethanolamine
Phosphatidylglycerol
Phosphatidylinositol
Phosphatidylcholine
Candida albicans
QD Chemistry
QH301 Biology
QR Microbiology
NDAS
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Abstract
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.
Citation
Cassilly , C D , Farmer , A T , Montedonico , A E , Smith , T K , Campagna , S R & Reynolds , T B 2017 , ' Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans ' , FEMS Yeast Research , vol. 17 , no. 2 , fox007 . https://doi.org/10.1093/femsyr/fox007
Publication
FEMS Yeast Research
Status
Peer reviewed
DOI
https://doi.org/10.1093/femsyr/fox007
ISSN
1567-1356
Type
Journal article
Rights
© 2017, FEMS. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at academic.oup.com / https://doi.org/10.1093/femsyr/fox007
Description
This work was supported by the National Institutes of Health NIH R01AL105690.
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  • University of St Andrews Research
URL
https://academic.oup.com/femsyr/article-lookup/doi/10.1093/femsyr/fox007#supplementary-data
URI
http://hdl.handle.net/10023/12664

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