ISOLATION OF VIRULENCE GENES DIRECTING GPI SYNTHESIS BY FUNCTIONAL COMPLEMENTATION OF LEISHMANIA

Recent advances in molecular genetics of Leishmania parasites prompted us to develop methods of functional genetic complementation in Leishm ania and apply them to the isolation of genes involved in the biosynth esis of the virulence determinant LPG, an abundant GPI-anchored polysa ccharide. LPG1, the gene product identified by complementation of our R2D2 LPG(-) mutant, may be a glycosyltransferase responsible for the a ddition of galactofuranose to the nascent chain. As galactofuranose is not found in mammalian cells, inhibition of the addition of this suga r could be exploited for chemotherapy. Overall, the success of the fun ctional complementation approach opens the way to the identification o f a variety of genes involved in pathogenesis and parasitism.