Nino-Vega, G.; Barreto, L.; Sorais, F.; Moreno, B.; San-Bias, G.
Intituto Venezolano de Investigaciones Cientificas (IVIC), Laboraiorio de Micologia, Apartado 21827. Caracas, 1020A, Venezuela. E-maii: firstname.lastname@example.org
Paracoccidioides brasilienxix, a thernlodimorphic fungus, is the causative agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America. Like in other pathogenic dimorphic fungi, its pathogenicity appears to be related to the dimorphic transition from the hyphal to the yeast form, which is triggered by a shift from environmental temperature to the temperature of the mammalian host. So far, information on genes necessary for the establishment and morphology of the pathogenic phase in R brasiliensis is not certain, although valuable and increasing information on genes preferentially expressed on this phase is been given by the groups working on the construction of expressed sequence tags (ESTs) libraries on this fungus (Yeast 20:263-271, 2003; Eukariotic Cell 2:34-48, 2003; MoI. Gen. Genomics 271:667-677, 2005; J. Biol. Chem. 280:24706-24714, 2005)
In this work, we present three genes expressed only in the pathogenic phase of P. brasiliensis, on which our group has been working in the last few years. Two of them (PbrAGSl, for alpha- 1,3-glucan synthase and PbrCHS3 for a class III chitin synthase) are related to the synthesis of cell wall components and are potentially involved in morphology and virulence of the fungus. Preliminary experimental data prompt us to speculate on a possible post-transcriptional regulation for PbrAGSl. The deduced product of the third gene, PbrCHPl, presents identity with a HiMopia.siua capsitlaium calcium binding protein (MoI. Microbiol. 27:531-539, 1998), involved in virulence in the yeast phase of this dimorphic fungus (Science 290:1368-1372, 2000). Also, our group has been working on the testing of several antifungal and potential anttfungal drugs, one of them caspofungin (Cancidas, Merck). To our surprise, caspofungin, a beta-1,3-glucan synthase inhibitor, affected not only the mycelial phase as expected, but also the yeast phase of P. brasilien.sis, despite the low amount of this glucan in the yeast cell wall. Micrographs show damage to the cell wall of the yeast phase. When we explored by northern the expression of one of two reported beta-1,3-glucan synthase genes, FAT1V/ (Yeast 16:451-462, 2000), we found to our surprise, that f-'KSI has a higher expression in the yeast phase than in the mycelial phase, which together with the results mentioned above from the caspofungin microbiological experiments, made us wonder if beta-1,3-glucan, even when represents a small percentage of the yeast cell wall components, would be essential for its maintenance.
Copyright Instituto de Medicina Tropical de Sao Paulo Oct 2005
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