INHIBITION OF PARACOCCIDIOIDES-BRASILIENSIS BY AJOENE IS ASSOCIATED WITH BLOCKADE OF PHOSPHATIDYLCHOLINE BIOSYNTHESIS

In Paracoccidioides brasiliensis, a dimorphic fungus pathogenic for hu mans, no significant differences were observed in the phospholipid spe cies of both morphological phases. The species observed were phosphati dylcholine (PC, 30-40%), phosphatidylethanolamine (PE, 27-28%), phosph atidylserine (16-19%), phosphatidylinositol (13-17%) and sphingomyelin (3-5%). The main fatty acids found in the yeast (Y) phase were palmit ate (56%), linoleate (18%) and oleate (15%), while linoleate predomina ted (61%) in the mycelial (M) phase, followed by palmitate (27%) and o leate (7%). In the Y phase the main free sterol was ergosta-5,22-dien- 3 beta-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-3 beta-ol (12%). Ajoene [(E,Z)-4,5,9-trithiadodec a-1,6,11-triene 8-oxide], a platelet aggregation inhibitor derived fro m garlic, induced alterations in phospholipid and fatty acid proportio ns such that PC was reduced to about 18% in both phases and PE increas ed to 38% (Y phase) or 44% (88 phase), suggesting inhibition of PC syn thesis. 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 unsatu rated components. This effect was not seen in the M phase.