Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis or South American blastomycosis. Many aspects of the disease and its agent are unknown. One of the most important factors regarding the infection and the host-parasite relationships seems to be the fungal cell wall whose biochemical aspects are reviewed here. Biochemical studies, done mainly by Kanetsuna et al., (21,22), have demonstrated that the yeastlike (Y) and the mycelial (M) forms have chitin as a common polysaccharide, with alpha-1, 3-glucan in the Y form and beta-1, 3-glucan in the M form. These polysaccharides are fibrillar and determine to some degree the fungal shape. Moreover, an amorphous galactomannan is found in the cell wall of the M form. This compound is responsible for the antigenic properties of the cell wall (1). Recent studies (30-33) suggest that the cell wall does not possess a stable chemical structure but a rather changing one, as a function of the environment in which the fungus is grown. At the same time, the cell wall composition seems to correlate with the degree of virulence of the particular strain. From these observations it may be deduced that the constituent polysaccharides of P. brasiliensis cell wall, play an important role in the active protection of the fungus against the defensive mechanisms of the host.
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 O h ) , p hosp hat idy let hanolami ne (PE, 27-28 O h ) , phosp hat id y lser i ne (16-19%), phosphatidylinositol (1347%) and sphingomyelin (3-50' 0). The main fatty acids found in the yeast (Y) phase were palmitate (56%), linoleate (18%) and oleate (15%), while linoleate predominated (61 YO) in the mycelial (M) phase, followed by palmitate (27 YO) and oleate (7 YO). In the Y phase the main free sterol was ergosta=5,22=dien=3/%ol (82 YO) plus some lanosterol (12 YO) and ergosterol (6%), while in the M phase, the latter predominated (88%), followed by low levels of ergosta-5,22-dien-3/%ol (12 YO). Ajoene [(€,2)-4,5,9-trithiadodeca-l,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:O and 18:O) 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.
The yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9 reduced the amount of a-1,3-glucan in its cell wall from 45 to 3% when subcultured in vitro for several years. This strain regained its a-1,3-glucan up to 25% of the total cell wall when grown in vivo. A mutant strain of P. brasiliensis Pb9, named IVIC Pbl4O, reported to have 1,3-mannan instead of a-glucan in the cell wall, could not be recovered from experimentally infected animals. The existence of some relationship between the presence of a-1,3-glucan in the cell wall of the yeastlike form and the pathogenicity of this fungus is suggested in this report.
A morphological mutant of Paracoccidioides brasiliensis strain IVIC ~b 9 was isolated after treatment of the yeast-like (Y) form with nitrosoguanidine. Colonies of the mutant grown at room temperature did not show the whitish cotton-like morphology typical of the mycelial form of the parental strain. Y-cells were much smaller than those produced by the parent and grew forming chains of different sizes. The main chemical difference in the wall of the Y-form was the replacement of the a-1,3-glucan, typical of the parental strain, by an amorphous 1,3-mannan in the mutant.
Ajoene, a garlic-derived compound that prevents platelet activation, inhibited the growth of Paracoccidioides brasiliensis, a fungal pathogen for humans, by affecting the integrity of the fungal cytoplasmic membrane. This action may be the basis for the study of ajoene as a possible specific antifungal drug.
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