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Published on: September 18, 2018
The ATP-binding cassette (ABC) gene family of Plasmodium falciparum
1The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Melbourne 3050, Australia.
Abstract:
Multidrug resistance (MDR) in mammalian tumour cells is mediated by P-glycoproteins. The apparent similarities between MDR and the chloroquine-resistance phenotype (CQR) in Plasmodium falciparum suggests that homologous proteins may be involved. In mammals, P-glycoproteins are encoded by mdr genes that are a subset of a super-family characterized by ATP-binding cassettes (ABC). Three genes, pfmdr1, pfmdr2 and pfef3-rl, have been identified in P. falciparum that have homology to the ABC transporter gene family. Each protein encoded by these genes has a distinct structure, suggesting functional differences between the three. Justin Rubio and Alan Cowman here discuss the structure and possible function of the ABC proteins from P. falciparum and evidence that the protein encoded by the pfmdr1 gene can influence quinoline-containing antimalarial drug-resistance phenotypes.
Insights
Multidrug resistance (MDR) in malaria parasites may involve proteins similar to those found in mammalian tumors. The pfmdr1 gene in Plasmodium falciparum is linked to resistance against certain antimalarial drugs.
Area of Science:
- Biochemistry
- Molecular Biology
- Parasitology
Background:
- Multidrug resistance (MDR) in mammalian tumor cells is associated with P-glycoproteins.
- Similarities between MDR and chloroquine resistance in Plasmodium falciparum suggest homologous proteins are involved.
- P-glycoprotein genes in mammals (mdr) belong to the ATP-binding cassette (ABC) transporter superfamily.
Purpose of the Study:
- To investigate homologous proteins in Plasmodium falciparum that may be involved in drug resistance.
- To explore the structure and function of ABC transporter proteins in P. falciparum.
- To examine the role of the pfmdr1 gene in antimalarial drug resistance.
Main Methods:
- Identification of three genes in P. falciparum (pfmdr1, pfmdr2, pfef3-rl) homologous to the ABC transporter gene family.
- Structural analysis of the encoded proteins to infer functional differences.
- Investigation of the influence of the pfmdr1 gene product on drug resistance phenotypes.
Main Results:
- Three P. falciparum genes (pfmdr1, pfmdr2, pfef3-rl) show homology to the ABC transporter gene family.
- Distinct protein structures suggest specialized functions for each encoded protein.
- Evidence indicates the protein encoded by pfmdr1 influences resistance to quinoline-based antimalarial drugs.
Conclusions:
- Homologous ABC transporter proteins likely play a role in drug resistance in Plasmodium falciparum.
- The pfmdr1 gene product is a key factor in mediating resistance to specific antimalarial drugs.
- Understanding these ABC proteins is crucial for developing strategies against drug-resistant malaria.
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