MULTIDRUG-RESISTANCE AND P-GLYCOPROTEINS IN PARASITIC PROTOZOA

Drug resistance has emerged as a devasting impediment to the treatment and control of diseases of parasitic origin. The underlying mechanism s that contribute to this drug resistance in field isolates, however, are poorly understood. Members of the P-glycoprotein gene (pgp) family have been identified, cloned, and sequenced in Plasmodia, Leishmania, and Entamoeba, and variations in pgp copy number and/or expression ha ve been implicated as a basis for drug resistance in each of these gen era. The spectrum of drugs to which parasitic protozoa containing ampl ified pgp genes and/or transcripts are refractory range from a phenoty pe similar to that observed with multidrug-resistant mammalian cells t o those that are completely distinct. The availability of molecular pr obes to pgp genes provides valuable reagents to dissect the role of pg p gene amplification and overexpression in mediating drug resistance i n parasitic protozoa and to determine the physiological function of P- glycoproteins in this clinically consequential group of human pathogen s.