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Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I

McLeod, R and Muench, S P and Rafferty, J B and Kyle, D E and Mui, E J and Kirisits, M J and Mack, D G and Roberts, C W and Samuel, B U and Lyons, R E and Dorris, M and Milhous, W K and Rice, D W (2001) Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I. International Journal for Parasitology, 31 (2). pp. 109-113. ISSN 0020-7519

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Abstract

Fab I, enoyl acyl carrier protein reductase (ENR), is an enzyme used in fatty acid synthesis. It is a single chain polypeptide in plants, bacteria, and mycobacteria, but is part of a complex polypeptide in animals and fungi. Certain other enzymes in fatty acid synthesis in apicomplexan parasites appear to have multiple forms, homologous to either a plastid, plant-like single chain enzyme or more like the animal complex polypeptide chain. We identified a plant-like Fab I in Plasmodium falciparum and modelled the structure on the Brassica napus and Escherichia coli structures, alone and complexed to triclosan (5-chloro-2-[2,4 dichlorophenoxy] phenol]), which confirmed all the requisite features of an ENR and its interactions with triclosan. Like the remarkable effect of triclosan on a wide variety of bacteria, this compound markedly inhibits growth and survival of the apicomplexan parasites P. falciparum and Toxoplasma gondii at low (i.e. IC50 congruent with150-2000 and 62 ng/ml, respectively) concentrations. Discovery and characterisation of an apicomplexan Fab I and discovery of triclosan as lead compound provide means to rationally design novel inhibitory compounds.

Item type: Article
ID code: 33627
Keywords: amino acid sequence, animals, antimalarials, enoyl-(acyl-carrier-protein) reductase (NADH), enzyme inhibitors, humans, models, molecular, molecular sequence data, oxidoreductases, plasmodium falciparum, sequence alignment, toxoplasma, triclosan, Pharmacy and materia medica, Infectious Diseases, Parasitology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 28 Sep 2011 16:01
    Last modified: 05 Sep 2014 11:00
    URI: http://strathprints.strath.ac.uk/id/eprint/33627

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