Arachidonic acid stimulates cell growth and forms a novel oxygenated metabolite in Candida albicans.
Infection of human tissues by Candida albicans has been reported to cause the release of arachidonic acid (AA), eicosanoids and other proinflammatory mediators from host cells. Therefore, we investigated the interaction of this pathogen with AA. AA stimulated cell growth at micromolar concentrations when used as a sole carbon source. Moreover, it selectively inhibited the antimycin A-resistant alternative oxidase. [1-(14)C]AA was completely metabolised by C. albicans. Only one-seventh of the radioactivity metabolised was found in CO(2), whereas two-thirds occurred in carbohydrates suggesting a predominant role of the glyoxalate shunt of citrate cycle. About 1% of radioactivity was found in polar lipids including eicosanoids. A novel AA metabolite, which revealed immunoreactivity with an antibody against 3(R)-hydroxy-oxylipins, was identified as 3, 18-dihydroxy-5,8,11,14-eicosatetraenoic acid. Using immunofluorescence microscopy, endogenous 3(R)-hydroxy-oxylipins were found in hyphae but not in yeast cells. Such compounds have recently been shown to be connected with the sexual stage of the life cycle of Dipodascopsis uninucleata. Together, we propose that infection-mediated release of AA from host cells may modulate cell growth, morphogenesis and invasiveness of C. albicans by several modes. A better understanding of its role is thus promising for novel approaches towards the treatment of human mycoses.
Deva
R
R
Department of Gynaecology, University Medical Centre Benjamin Franklin, Free University of Berlin, Germany.
Ciccoli
R
R
Schewe
T
T
Kock
J L
JL
Nigam
S
S
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002250:Carbon Radioisotopes; D002455:Cell Division / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D024101:Mitochondrial Proteins; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010940:Plant Proteins; D020156:Salicylic Acid / Q000494:pharmacology; D000099188:Alternative Oxidase
D016718:Arachidonic Acid; D002250:Carbon Radioisotopes; D006893:Hydroxyeicosatetraenoic Acids; D019787:Linoleic Acid; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D020156:Salicylic Acid; D000099188:Alternative Oxidase