Multiple drug resistance genes in malaria -- from epistasis to epidemiology.

Abstract:

:A decline in our ability to successfully treat patients with malaria infections of the parasitic protozoan Plasmodium falciparum with cheap quinoline drugs has led to a huge escalation in morbidity and mortality in recent years. Many approaches have been taken, including classical genetics, reverse genetics and molecular epidemiology, to identify the molecular determinants underlying this resistance. The contribution of the P. falciparum multidrug resistance gene, pfmdr1, to antimalarial resistance has been a source of controversy for over a decade since it was first identified. In the current issue of Molecular Microbiology, Sidhu and colleagues use powerful reverse genetics to demonstrate the importance of commonly occurring alleles of pfmdr1 in conferring resistance to the second-line drugs quinine and sensitivity to the new alternatives mefloquine and artemisinin. They also elegantly highlight the importance of genetic background and epistasis between pfmdr1 and other potential modulators of drug resistance. Such molecular knowledge will facilitate surveillance/monitoring and aid the development of strategies for the reversal of resistance.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Duraisingh MT,Refour P

doi

10.1111/j.1365-2958.2005.04748.x

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

874-7

issue

4

eissn

0950-382X

issn

1365-2958

pii

MMI4748

journal_volume

57

pub_type

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