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The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens

Williams, Catrin Ffion, Vacca, A. R., Dunham, L., Lloyd, David, Coogan, M. P., Evans, G., Graz, M. and Cable, Joanne 2016. The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens. Molecular and Biochemical Parasitology 206 (1-2) , pp. 20-28. 10.1016/j.molbiopara.2016.03.001

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Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40 μg/ml against S. vortens. GC–MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16 μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4 μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected Pterophyllum scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0166-6851
Funders: Engineering and Physical Sciences Research Council
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 4 March 2016
Last Modified: 02 Mar 2021 02:28

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