Adaptation of Plasmodium falciparum to glucose 6-phosphate dehydrogenase-deficient host red cells by production of parasite-encoded enzyme

Abstract

There is impressive evidence from geographical data^1,2, studies in the field³ and in vitro culture work^4–6 that genetically determined deficiency of glucose 6-phosphate dehydrogenase (G6PD) confers relative protection against the human malaria parasite, Plasmodium falciparum. G6PD is encoded by an X-chromosome-linked gene⁷, and protection phenomenon is manifested in heterozygous females who are genetic mosaics but, surprisingly, not in hemizygous males with complete deficiency⁸. We have shown previously that the parasite, when passaged serially through G6PD-deficient red cells, undergoes adaptive changes that gradually improve its ability to multiply in these deficient cells⁹. To explain the above paradox, we now show that this adaptive process is associated with, and may consist in, the induction of synthesis of a novel G6PD coded by Plasmodium falciparum.