Physiology and molecular genetics of multidrug resistance in Entamoeba histolytica

Abstract

Entamoeba histolytica presents the evolutionarily conserved multidrug- resistance (MDR) phenotype, discovered in mammalian cells. MDR cells overexpress the membrane P-glycoprotein, which excludes unrelated drugs from the cytoplasm. E histolytica mutants exhibit cross-resistance to unrelated drugs, which are pumped out from the cytoplasm. In drug-resistant trophozoites, the constitutively expressed EhPg1 gene appears to be up- regulated by a C/EBP-like factor and a multiprotein complex that were not found in drug-sensitive trophozoites. The drug-induced EhPgp5 gene, on the other hand, appears to be up-regulated by AP-1 and HOX factors. Here we review the main physiological and molecular facts of the MDR phenotype in E. histolytica.