Physiological aspects of nitro drug resistance in Giardia lamblia

Müller, Joachim; Hemphill, Andrew; Müller, Norbert (2018). Physiological aspects of nitro drug resistance in Giardia lamblia. International journal for parasitology. Drugs and drug resistance, 8(2), pp. 271-277. Elsevier 10.1016/j.ijpddr.2018.04.008

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For over 50 years, metronidazole and other nitro compounds such as nitazoxanide have been used as a therapy of choice against giardiasis and more and more frequently, resistance formation has been observed. Model systems allowing studies on biochemical aspects of resistance formation to nitro drugs are, however, scarce since resistant strains are often unstable in culture. In order to fill this gap, we have generated a stable metronidazole- and nitazoxanide-resistant Giardia lamblia WBC6 clone, the strain C4. Previous studies on strain C4 and the corresponding wild-type strain WBC6 revealed marked differences in the transcriptomes of both strains. Here, we present a physiological comparison between trophozoites of both strains with respect to their ultrastructure, whole cell activities such as oxygen consumption and resazurin reduction assays, key enzyme activities, and several metabolic key parameters such as NAD(P)+/NAD(P)H and ADP/ATP ratios and FAD contents. We show that nitro compound-resistant C4 trophozoites exhibit lower nitroreductase activities, lower oxygen consumption and resazurin reduction rates, lower ornithine-carbamyl-transferase activity, reduced FAD and NADP(H) pool sizes and higher ADP/ATP ratios than wildtype trophozoites. The present results suggest that resistance formation against nitro compounds is correlated with metabolic adaptations resulting in a reduction of the activities of FAD-dependent oxidoreductases.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
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:

Müller, Joachim; Hemphill, Andrew and Müller, Norbert

Subjects:

600 Technology > 630 Agriculture

ISSN:

2211-3207

Publisher:

Elsevier

Language:

English

Submitter:

Monika Mumenthaler

Date Deposited:

17 Dec 2018 08:46

Last Modified:

17 Dec 2018 08:47

Publisher DOI:

10.1016/j.ijpddr.2018.04.008

PubMed ID:

29738984

BORIS DOI:

10.7892/boris.122102

URI:

https://boris.unibe.ch/id/eprint/122102

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