Physiology and molecular genetics of multidrug resistance in Entamoeba histolytica

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-I and HOX factors. Here we review the main physiological and molecular facts of the MDR phenotype in E histolvtica.