Multiple drug resistance in the pathogenic protozoa

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.