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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Expression and function of pvcrt-o, a Plasmodium vivax ortholog of pfcrt, in Plasmodium falciparum and Dictyostelium discoideum
Molecular and Biochemical Parasitology, Volume 150, No. 2, Year 2006
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Description
Chloroquine resistance in Plasmodium vivax threatens the use of this drug as first-line treatment for millions of people infected each year worldwide. Unlike Plasmodium falciparum, in which chloroquine resistance is associated with mutations in the pfcrt gene encoding a digestive vacuole transmembrane protein, no point mutations have been associated with chloroquine resistance in the P. vivax ortholog gene, pvcrt-o (also called pvcg10). However, the question remains whether pvcrt-o can affect chloroquine response independent of mutations. Since P. vivax cannot be cultured in vitro, we used two heterologous expression systems to address this question. Results from the first system, in which chloroquine sensitive P. falciparum parasites were transformed with pvcrt-o, showed a 2.2-fold increase in chloroquine tolerance with pvcrt-o expression under a strong promoter; this effect was reversed by verapamil. In the second system, wild type pvcrt-o or a mutated form of the gene was expressed in Dictyostelium discoideum. Forms of PvCRT-o engineered to express either lysine or threonine at position 76 produced a verapamil-reversible reduction of chloroquine accumulation in this system to ∼60% of that in control cells. Our data support an effect of PvCRT-o on chloroquine transport and/or accumulation by P. vivax, independent of the K76T amino acid substitution. © 2006 Elsevier B.V. All rights reserved.
Authors & Co-Authors
Sa, Juliana Martha
Brazil, Sao Paulo
Universidade de São Paulo
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Yamamoto, Marcio Massao
Brazil, Sao Paulo
Universidade de São Paulo
Fernandez-Becerra, C.
Brazil, Sao Paulo
Universidade de São Paulo
de Azevedo, Mauro Ferreira
Brazil, Sao Paulo
Universidade de São Paulo
Papakrivos, Janni
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Naudé, Bronwen
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
South Africa, Cape Town
University of Cape Town
Wellems, Thomas E.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Del Portillo, Hernando A.
Brazil, Sao Paulo
Universidade de São Paulo
Statistics
Citations: 58
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1016/j.molbiopara.2006.08.006
ISSN:
01666851
Research Areas
Genetics And Genomics