Nitroreductase (GlNR1) increases susceptibility of Giardia lamblia and Escherichia coli to nitro drugs

Nillius, Dorothea; Müller, Joachim; Müller, Norbert (2011). Nitroreductase (GlNR1) increases susceptibility of Giardia lamblia and Escherichia coli to nitro drugs. Journal of antimicrobial chemotherapy, 66(5), pp. 1029-35. Oxford: Oxford University Press 10.1093/jac/dkr029

Preview

Text dkr029.pdf - Published Version Available under License Publisher holds Copyright. Download (422kB) | Preview

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.

Interest & Impact

Downloads

164 since deposited on 04 Oct 2013
29 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item