IDENTIFICATION OF GENES MEDIATING LIPOPHOSPHOGLYCAN BIOSYNTHESIS BY FUNCTIONAL COMPLEMENTATION OF LEISHMANIA-DONOVANI MUTANTS

A powerful approach for identifying the genes involved in the infectio us cycle of pathogens is functional genetic complementation. Here, the current status of this technology in Leishmania is reviewed, focusing on the genes involved in the biosynthesis of the unique parasite surf ace glycolipid, lipophosphoglycan (LPG). LPG plays multiple roles in t he Leishmania infectious cycle, in both the sand ny vector and in esta blishing successful intracellular parasitism within the vertebrate mac rophage. The emerging methods for generating LPG mutations and for rec overing the affected gene(s) by complementation with an episomal genom ic Leishmania DNA library are reviewed. The properties and probable ro les of the first two genes identified by this methodology are discusse d. These methods also show great promise in the search for genes affec ting other virulence factors of Leishmania as well as in the identific ation of new drug-resistance loci.