Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum.
The antimicrobial biocide triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol] potently inhibits the growth of Plasmodium falciparum in vitro and, in a mouse model, Plasmodium berghei in vivo. Inhibition of [14C]acetate and [14C]malonyl-CoA incorporation into fatty acids in vivo and in vitro, respectively, by triclosan implicate FabI as its target. Here we demonstrate that the enoyl-ACP reductase purified from P. falciparum is triclosan sensitive. Also, we present the evidence for the existence of FabI gene in P. falciparum. We establish the existence of the de novo fatty acid biosynthetic pathway in this parasite, and identify a key enzyme of this pathway for the development of new antimalarials.
Surolia
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Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India.
Surolia
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D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004195:Disease Models, Animal; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D005227:Fatty Acids / Q000096:biosynthesis; D008288:Malaria / Q000469:parasitology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D014260:Triclosan / Q000494:pharmacology*
D000962:Antimalarials; D005227:Fatty Acids; D009243:NAD; D014260:Triclosan; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)