Import of host delta-aminolevulinate dehydratase into the malarial parasite: Identification of a new drug target

The parasite Plasmodium berghei imports the enzyme delta -aminolevulinate d ehydratase (ALAD), and perhaps the subsequent enzymes of the pathway from t he host red blood cell to sustain heme synthesis. Here we have studied the mechanism of this import. A 65-kDa protein on the P. berghei membrane speci fically bound to mouse red blood cell ALAD, and a 93-amino-acid fragment (A LAD-Delta NC) of the host erythrocyte ALAD was able to compete with the ful l-length enzyme for binding to the P. berghei membrane. ALAD-Delta NC was t aken up by the infected red blood cell when added to a culture of P. falcip arum and this led to a substantial decrease in ALAD protein and enzyme acti vity and, subsequently, heme synthesis in the parasite, resulting in its de ath.