Malaria drug resistance is associated with defective DNA mismatch repair

► Direct evidence of DNA mismatch repair activity in Plasmodium falciparum. ► Multi-drug resistant parasite strains possess defective DNA mismatch repair. ► Lack of PfMLH1 expression is the source of mismatch repair deficiency for W2 strain parasites. ► This study provides an exciting new hypothesis to explain the underlying mechanisms of P. falciparum drug resistance.