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 [ 14 C]acetate and [ 14 C]malonyl-CoA incorporation into fatty acids in vivo and in vitro , re...

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Veröffentlicht in:Nature medicine 2001-02, Vol.7 (2), p.167-173
Hauptverfasser: Surolia, Namita, Surolia, Avadhesha
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Sprache:eng
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Zusammenfassung: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 [ 14 C]acetate and [ 14 C]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.
ISSN:1078-8956
1546-170X
DOI:10.1038/84612