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Infection and Immunity, July 2007, p. 3498-3505, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00232-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Characterization of Prostaglandin E2 Production by Candida albicans{triangledown}

John R. Erb-Downward1 and Mairi C. Noverr2*

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0642,1 Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 482012

Received 12 February 2007/ Returned for modification 3 March 2007/ Accepted 23 April 2007

Candida albicans produces lipid metabolites that are functionally similar to host prostaglandins. These studies, using mass spectrometry, demonstrate that C. albicans produces authentic prostaglandin E2 (PGE2) from arachidonic acid. Maximal PGE2 production was achieved at 37°C in stationary-phase culture supernatants and in cell-free lysates generated from stationary-phase cells. Interestingly, PGE2 production is inhibited by both nonspecific cyclooxygenase and lipoxygenase inhibitors but not by inhibitors specific for the cyclooxygenase 2 isoenzyme. The C. albicans genome does not possess a cyclooxygenase homolog; however, several genes that may play a role in prostaglandin production from C. albicans were investigated. It was found that a C. albicans fatty acid desaturase homolog (Ole2) and a multicopper oxidase homolog (Fet3) play roles in prostaglandin production, with ole2/ole2 and fet3/fet3 mutant strains exhibiting reduced PGE2 levels compared with parent strains. This work demonstrates that the synthesis of PGE2 in C. albicans proceeds via novel pathways.

* Corresponding author. Mailing address: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201. Phone: (313) 577-9746. Fax: (313) 577-1155. E-mail: mnoverr{at}med.wayne.edu

{triangledown} Published ahead of print on 30 April 2007.

Editor: A. Casadevall

Infection and Immunity, July 2007, p. 3498-3505, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00232-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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