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Nitroreductase (GlNR1) Increases Susceptibility of Giardia Lamblia and Escherichia Coli to Nitro Drugs

Nitroreductase (GlNR1) Increases Susceptibility of Giardia Lamblia and Escherichia Coli to Nitro Drugs

Dorothea Nillius, Joachim Müller, Norbert Müller

J Antimicrob Chemother. 2011 May;66(5):1029-35.

PMID: 21393225

Abstract:

Objectives:
The protozoan parasite Giardia lamblia causes the intestinal disease giardiasis, which may lead to acute and chronic diarrhoea in humans and various animal species. For treatment of this disease, several drugs such as the benzimidazole albendazole, the nitroimidazole metronidazole and the nitrothiazolide nitazoxanide are currently in use. Previously, a G. lamblia nitroreductase 1 (GlNR1) was identified as a nitazoxanide-binding protein. The aim of the present project was to elucidate the role of this enzyme in the mode of action of the nitro drugs nitazoxanide and metronidazole.
Methods:
Recombinant GlNR1 was overexpressed in both G. lamblia and Escherichia coli (strain BL21). The susceptibility of the transfected bacterial and giardial cell lines to nitazoxanide and metronidazole was analysed.
Results:
G. lamblia trophozoites overexpressing GlNR1 had a higher susceptibility to both nitro drugs. E. coli were fully resistant to nitazoxanide under both aerobic and semi-aerobic growth conditions. When grown semi-aerobically, bacteria overexpressing GlNR1 became susceptible to nitazoxanide.
Conclusions:
These findings suggest that GlNR1 activates nitro drugs via reduction yielding a cytotoxic product.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415149	Nitroreductase from Escherichia coli			Price

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