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Physiological aspects of nitro drug resistance in Giardia lamblia.
- Source :
-
International journal for parasitology. Drugs and drug resistance [Int J Parasitol Drugs Drug Resist] 2018 Aug; Vol. 8 (2), pp. 271-277. Date of Electronic Publication: 2018 Apr 28. - Publication Year :
- 2018
-
Abstract
- 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) <superscript>+</superscript> /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.<br /> (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Antiparasitic Agents pharmacology
Antiprotozoal Agents pharmacology
Giardia lamblia enzymology
Giardia lamblia ultrastructure
Giardiasis drug therapy
Giardiasis parasitology
Nitro Compounds pharmacology
Nitroreductases metabolism
Oxidoreductases metabolism
Oxygen metabolism
Trophozoites drug effects
Trophozoites physiology
Trophozoites ultrastructure
Drug Resistance physiology
Giardia lamblia drug effects
Giardia lamblia physiology
Metronidazole pharmacology
Nitro Compounds metabolism
Thiazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-3207
- Volume :
- 8
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal for parasitology. Drugs and drug resistance
- Publication Type :
- Academic Journal
- Accession number :
- 29738984
- Full Text :
- https://doi.org/10.1016/j.ijpddr.2018.04.008