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Metabolic changes in Giardia intestinalis during differentiation
T A Paget1, P T Macechko, E L Jarroll
1Department of Biology, Cleveland State University, Ohio 44115, USA.
The Journal of Parasitology
|May 12, 1998
Summary
Giardia spp. encystation alters oxygen uptake and metronidazole (MTZ) sensitivity. Oxygen consumption initially increases then drops, with MTZ resistance developing during cyst formation and reversing upon excystation.
Area of Science:
- Microbiology
- Parasitology
- Biochemistry
Background:
- Giardia spp. trophozoites are sensitive to metronidazole (MTZ), a key therapeutic drug.
- Cysts of Giardia spp. exhibit reduced oxygen uptake and MTZ sensitivity compared to trophozoites.
- The precise timing of these metabolic and sensitivity changes during encystation is not well understood.
Purpose of the Study:
- To determine when during the encystation process Giardia spp. cysts develop reduced oxygen uptake and MTZ resistance.
- To investigate changes in glucose and aspartate transport during encystation.
- To understand the metabolic basis for MTZ resistance in encysting Giardia.
Main Methods:
- Culturing Giardia spp. under encystation-inducing conditions.
- Measuring oxygen uptake rates at various time points during encystation.
- Assessing glucose and deoxy-D-glucose uptake using radiolabeled tracers.
- Evaluating aspartate uptake rates.
- Determining metronidazole (MTZ) sensitivity by measuring oxygen uptake inhibition.
Main Results:
- Oxygen uptake rates in Giardia spp. initially increased during early encystation (0-5 hr) then significantly decreased by 12 hr and 50 hr.
- Glucose uptake and stimulation of oxygen uptake by glucose decreased markedly after 12 hr of encystation.
- Deoxy-D-glucose uptake dropped significantly, while aspartate uptake remained relatively constant.
- Metronidazole (MTZ) resistance developed by 8 hr into encystation, coinciding with decreased oxygen uptake.
- Excystation rapidly restored both oxygen uptake and MTZ sensitivity within 30 minutes.
Conclusions:
- Giardia spp. undergo significant metabolic shifts during encystation, including altered glucose transport and reduced oxygen consumption.
- The development of MTZ resistance is linked to these metabolic changes, potentially involving the pyruvate ferredoxin oxidoreductase pathway.
- These findings provide insights into the survival mechanisms of Giardia spp. and the dynamics of drug resistance during its life cycle.