title: Novel K540N mutation in Plasmodium falciparum dihydropteroate synthetase confers a lower level of sulfa drug resistance than does a K540E mutation.
abstract: Sulfadoxine (SDX) and sulfamethoxazole (SMX) each inhibit the Plasmodium falciparum dihydropteroate synthetase (PfDHPS), and certain point mutations in this enzyme yield the drug-resistant parasite. Using a simple Escherichia coli model system, we describe here the effect of the recently reported novel K540N mutation in PfDHPS on the level of SDX/SMX resistance. The survival rate of the transformed E. coli (DHPS-deficient strain) under different SDX or SMX concentrations revealed that the K540N mutation confers a lower level of drug resistance than its contemporary K540E mutation. Further, SMX was more effective than SDX in the E. coli system.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Vanshika
authors.initials: V
authors.lastname: Lumb
authors.forename: Yagya D
authors.initials: YD
authors.lastname: Sharma
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D020128:Inhibitory Concentration 50; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D013413:Sulfadoxine / Q000494:pharmacology*; D013420:Sulfamethoxazole / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase; D013420:Sulfamethoxazole