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Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum

Nature Medicine volume 7, pages 167–173 (2001)Cite this article

A Correction to this article was published on 01 May 2001

Abstract

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.

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Figure 1: In vitro antimalarial activity of triclosan.
Figure 2: Inhibition of fatty acid synthesis by triclosan.
Figure 3: Enoyl-ACP reductase of P. falciparum.
Figure 4: FabI gene of the parasite.

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Acknowledgements

We thank D. Kamalapriya, T.R. Nagaraja, M. Kapoor, K. Bachhawat, A. Gupta, Kalyani and C. Thomas for technical support; N. Valsala for typographical assistance; R. Uday Kumar for helpful discussions; C.N.R. Rao and G. Padmanaban for encouragement; R. Mula for the gift of triclosan; and the Jawaharlal Nehru Centre for Advanced Scientific Research for financial help. Sequencing of P. falciparum chromosome BLOB was accomplished as part of the Malaria Genome Project with support by The Wellcome Trust.

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  1. Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India

    Namita Surolia

  2. Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India

    Avadhesha Surolia

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  1. Namita Surolia
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Correspondence to Avadhesha Surolia.

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Surolia, N., Surolia, A. Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat Med 7, 167–173 (2001). https://doi.org/10.1038/84612

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