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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Nillius, Dorothea; Müller, Joachim and Müller, Norbert

Subjects:

600 Technology > 630 Agriculture

ISSN:

0305-7453

Publisher:

Oxford University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:31

Last Modified:

29 Oct 2019 15:51

Publisher DOI:

10.1093/jac/dkr029

PubMed ID:

21393225

Web of Science ID:

000289584000012

BORIS DOI:

10.7892/boris.12111

URI:

https://boris.unibe.ch/id/eprint/12111 (FactScience: 218393)

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