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

R McLeod, S P Muench, J B Rafferty, D E Kyle, E J Mui, M J Kirisits, D G Mack, C W Roberts, B U Samuel, R E Lyons, M Dorris, W K Milhous, D W Rice

Research output: Contribution to journalArticle

167 Citations (Scopus)

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.
LanguageEnglish
Pages109-113
Number of pages5
JournalInternational Journal for Parasitology
Volume31
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Triclosan
Toxoplasma
Plasmodium falciparum
Growth
Peptides
Parasites
Enzymes
Fatty Acids
Acyl Carrier Protein
Bacteria
Brassica napus
Plastids
Mycobacterium
Inhibitory Concentration 50
Oxidoreductases
Fungi
Escherichia coli

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

Cite this

McLeod, R ; Muench, S P ; Rafferty, J B ; Kyle, D E ; Mui, E J ; Kirisits, M J ; Mack, D G ; Roberts, C W ; Samuel, B U ; Lyons, R E ; Dorris, M ; Milhous, W K ; Rice, D W. / Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I. In: International Journal for Parasitology. 2001 ; Vol. 31, No. 2. pp. 109-113.
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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.",
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McLeod, R, Muench, SP, Rafferty, JB, Kyle, DE, Mui, EJ, Kirisits, MJ, Mack, DG, Roberts, CW, Samuel, BU, Lyons, RE, Dorris, M, Milhous, WK & Rice, DW 2001, 'Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I' International Journal for Parasitology, vol. 31, no. 2, pp. 109-113. https://doi.org/10.1016/S0020-7519(01)00111-4

Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I. / McLeod, R; Muench, S P; Rafferty, J B; Kyle, D E; Mui, E J; Kirisits, M J; Mack, D G; Roberts, C W; Samuel, B U; Lyons, R E; Dorris, M; Milhous, W K; Rice, D W.

In: International Journal for Parasitology, Vol. 31, No. 2, 2001, p. 109-113.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I

AU - McLeod, R

AU - Muench, S P

AU - Rafferty, J B

AU - Kyle, D E

AU - Mui, E J

AU - Kirisits, M J

AU - Mack, D G

AU - Roberts, C W

AU - Samuel, B U

AU - Lyons, R E

AU - Dorris, M

AU - Milhous, W K

AU - Rice, D W

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - amino acid sequence

KW - animals

KW - antimalarials

KW - enoyl-(acyl-carrier-protein) reductase (NADH)

KW - enzyme inhibitors

KW - humans

KW - models, molecular

KW - molecular sequence data

KW - oxidoreductases

KW - plasmodium falciparum

KW - sequence alignment

KW - toxoplasma

KW - triclosan

U2 - 10.1016/S0020-7519(01)00111-4

DO - 10.1016/S0020-7519(01)00111-4

M3 - Article

VL - 31

SP - 109

EP - 113

JO - International Journal for Parasitology

T2 - International Journal for Parasitology

JF - International Journal for Parasitology

SN - 0020-7519

IS - 2

ER -