Plasmodium vivax dihydrofolate reductase as a target of sulpha drugs.

Liselotte Yimga Djapa (1) , Ruth Zelikson , Agnes Delahodde (1) , Monique Bolotin-Fukuhara (1) , André Mazabraud (2, 3, 4)

1 IGM - Institut de génétique et microbiologie [Orsay]
2 DE - Développement et évolution
3 CGM - Centre de génétique moléculaire
4 MAOAC - Mécanismes adaptatifs : des organismes aux communautés

Sulpha drugs act as competitive inhibitors of p-amino benzoic acid, an intermediate in the de novo folate pathway. Dihydropteroate synthase condenses sulpha drugs into sulpha-dihydropteroate (sulpha-DHP), which competes with dihydrofolate, the dihydrofolate reductase (DHFR) substrate. This designates DHFR as a possible target of sulpha-DHP. We suggest here that Plasmodium vivax DHFR is indeed the in vivo target of sulpha drugs. The wild-type DHFR expressed in Saccharomyces cerevisiae leads to cell growth inhibition, while sensitivity to the drug is exacerbated in the mutants. Contrary to what is observed with sulphanilamide, methotrexate is less effective on P. vivax-DHFR mutants than on wild-type mutant.

Domaines: Microbiologie et Parasitologie

Liselotte Yimga Djapa, Ruth Zelikson, Agnes Delahodde, Monique Bolotin-Fukuhara, André Mazabraud. Plasmodium vivax dihydrofolate reductase as a target of sulpha drugs.. FEMS Microbiology Letters, 2006, 256 (1), pp.105-11. ⟨10.1111/j.1574-6968.2005.00095.x⟩. ⟨hal-00283677⟩