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Published on: August 19, 2014
Pentamidine transport and sensitivity in brucei-group trypanosomes
The Journal of Protozoology
|May 1, 1976
Summary
Trypanosoma parasites show varying sensitivity to the drug pentamidine. Differences in how parasites transport pentamidine explain these variations in drug sensitivity.
Area of Science:
- Parasitology
- Molecular Biology
- Pharmacology
Background:
- Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense are protozoan parasites causing significant human and animal diseases.
- Pentamidine is a crucial drug for treating these trypanosomiases, but resistance is a growing concern.
- Understanding the mechanisms of drug uptake and resistance is vital for effective treatment strategies.
Purpose of the Study:
- To investigate the relationship between pentamidine transport kinetics and drug sensitivity in different forms and strains of Trypanosoma.
- To elucidate the role of dyskinetoplasty in pentamidine resistance.
- To compare pentamidine uptake and sensitivity across various developmental stages and subspecies of Trypanosoma.
Main Methods:
- In vitro drug sensitivity assays.
- Analysis of pentamidine transport kinetics using [3H]pentamidine.
- Comparison of uptake parameters (Km, Vmax) in bloodstream and culture forms of T. b. brucei and T. b. rhodesiense.
- Examination of drug-resistant strains and dyskinetoplastic forms.
Main Results:
- Significant differences in pentamidine sensitivity and transport were observed between T. b. brucei and T. b. rhodesiense.
- Long slender bloodstream forms of T. b. brucei exhibited high pentamidine affinity and uptake rates.
- Drug-resistant strains and T. b. rhodesiense showed reduced pentamidine transport rates.
- Procyclic trypomastigotes demonstrated the lowest sensitivity and a high capacity for drug exclusion.
- Dyskinetoplasty was not directly correlated with pentamidine resistance or altered transport.
Conclusions:
- Pentamidine transport mechanisms are key determinants of drug sensitivity in Trypanosoma parasites.
- Variations in uptake kinetics explain differential responses to pentamidine among parasite forms and strains.
- Procyclic trypomastigotes possess intrinsic mechanisms for excluding pentamidine, contributing to their resistance.
- Dyskinetoplasty is not a direct cause of pentamidine resistance in Trypanosoma.
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