Inhibition of Paracoccidioides brasiliensis by ajoene is associated with blockade of phosphatidylcholine biosynthesis

摘要

In Paracoccidioides brasiliensis, a dimorphic fungus pathogenic for humans, no significant differences were observed in the phospholipid species of both morphological phases. The species observed were phosphatidylcholine (PC, 30-40%), phosphatidylethanolamine (PE, 27-28%), phosphatidylserine (16-19%), phosphatidylinositol (13-17%) and sphingomyelin (3-5%). The main fatty acids found in the yeast (Y) phase were palmitate (56%), linoleate (18%) and oleate (15%), while linoleate predominated (61 %) in the mycelial (M) phase, followed by palmitate (27%) and oleate (7%). In the Y phase the main free sterol was ergosta-5,22-dien-3β-ol (82%) plus some lanosterol (12%) and ergosterol (6%), while in the M phase, the latter predominated (88%), followed by low levels of ergosta-5,22-dien-3β-ol (12%). Ajoene [(E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide], a platelet aggregation inhibitor derived from garlic, induced alterations in phospholipid and fatty acid proportions such that PC was reduced to about 18% in both phases and PE increased to 38% (Y phase) or 44% (M phase), suggesting inhibition of PC synthesis. Ajoene also reduced saturated fatty acids (16:0 and 18:0) from 67 to 35% in the Y phase, with a corresponding increase in the unsaturated components. This effect was not seen in the M phase.