DHFR and malaria: For instance, in Plasmodium falciparum (malaria parasites), antifolate drug resistance involves point mutations in dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) [84]; mutations in the Kelch13 protein (K13), involved in multiple intracellular processes including hemoglobin catabolism, are associated with artemisinin resistance [67,68]; and overexpression or mutations in the digestive vacuole membrane-bound ABC transporter PfMDR1 are associated with resistance to chloroquine and other 4-aminoquinolines [69,70].