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Multiple drug resistance in the pathogenic protozoa
1Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
Abstract:
Evidence for the phenomenon of multiple drug resistance (MDR) in the well studied pathogenic protozoa has been examined. This has been placed in the more familiar context of the MDR efflux transporters and the cloned mdr genes of mammalian cells. Homologues of the mdr gene family in protozoa and their possible role in drug efflux have been compared with their mammalian counterparts. Possible mechanisms and models for drug efflux have been considered. The unusual and extensive range of substrates transported by the ATP-binding cassette (ABC) family of transporters which includes the MDRs has been raised. The impact of kinetics, structure and bioenergetics of the MDR family members on mechanisms of transport has been accentuated to argue that MDR efflux considered in isolation appears bizarre but may be better understood in a broader context.
Insights
Multiple drug resistance (MDR) in pathogenic protozoa is examined, comparing their mdr genes and efflux transporters to mammalian counterparts. Understanding MDR in protozoa requires a broader context of ATP-binding cassette (ABC) transporters.
Area of Science:
- Molecular Biology
- Parasitology
- Biochemistry
Background:
- Multiple drug resistance (MDR) is a significant challenge in treating pathogenic protozoa.
- MDR efflux transporters and their associated mdr genes are well-characterized in mammalian cells.
- Protozoan MDR mechanisms share similarities with, yet possess unique characteristics compared to, mammalian systems.
Purpose of the Study:
- To examine evidence for MDR in pathogenic protozoa.
- To compare protozoan mdr gene homologues and their roles in drug efflux with mammalian MDR systems.
- To explore the broader context of ATP-binding cassette (ABC) transporters in understanding MDR.
Main Methods:
- Comparative analysis of mdr gene families in protozoa and mammals.
- Review of existing evidence on drug efflux mechanisms in pathogenic protozoa.
- Examination of the substrate range, kinetics, structure, and bioenergetics of MDR transporters.
Main Results:
- Evidence for MDR phenomena in pathogenic protozoa is presented.
- Homologues of the mdr gene family in protozoa are identified and compared to mammalian MDR.
- The broad substrate specificity of ATP-binding cassette (ABC) transporters, including MDRs, is highlighted.
Conclusions:
- MDR in protozoa shares characteristics with mammalian MDR, involving efflux transporters and mdr genes.
- A comprehensive understanding of protozoan MDR necessitates considering the broader family of ABC transporters.
- The complex transport mechanisms of MDR efflux transporters are better understood within a wider biological context.