1. Parallel evolution of adaptive mutations in Plasmodium falciparum mitochondrial DNA during atovaquone-proguanil treatment
- Author
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Lise Musset, Jérôme Clain, Jacques Le Bras, EA 209 - Transports membranaires et chimiorésistances (LABORATOIRE DE PARASITOLOGIE-MYCOLOGIE), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) - AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
MESH : Molecular Sequence Data ,MESH : Cytochromes b ,DNA Mutational Analysis ,Drug Resistance ,MESH: Base Sequence ,MESH: Parasitic Sensitivity Tests ,MESH : Malaria, Falciparum ,Parasitic Sensitivity Tests ,MESH : Biological Evolution ,MESH : DNA, Mitochondrial ,MESH : Proguanil ,Genotype ,MESH : Plasmodium falciparum ,MESH : Parasitic Sensitivity Tests ,MESH: Animals ,Malaria, Falciparum ,MESH: DNA Mutational Analysis ,MESH: Plasmodium falciparum ,Genetics ,0303 health sciences ,biology ,Cytochrome b ,MESH: Malaria, Falciparum ,Cytochromes b ,MESH: Proguanil ,MESH: Cytochromes b ,Biological Evolution ,3. Good health ,Proguanil ,MESH: Drug Resistance ,MESH : Atovaquone ,MESH : Mutation ,[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,medicine.drug ,Mitochondrial DNA ,MESH: Mutation ,Molecular Sequence Data ,Plasmodium falciparum ,MESH: Atovaquone ,MESH: Biological Evolution ,MESH : DNA Mutational Analysis ,DNA, Mitochondrial ,MESH: Sequence Homology, Nucleic Acid ,Antimalarials ,03 medical and health sciences ,Sequence Homology, Nucleic Acid ,medicine ,Animals ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,MESH : Sequence Homology, Nucleic Acid ,Allele ,Molecular Biology ,Gene ,Atovaquone ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,MESH : Drug Resistance ,MESH: Molecular Sequence Data ,MESH: Humans ,Base Sequence ,030306 microbiology ,MESH : Humans ,Haplotype ,MESH: DNA, Mitochondrial ,biology.organism_classification ,Atovaquone/proguanil ,MESH: Antimalarials ,Mutation ,MESH : Antimalarials ,MESH : Base Sequence ,MESH : Animals - Abstract
International audience; Here we provide direct evidence that two adaptive nucleotide changes in the same codon (268) of the cytochrome b gene (pfcytb) each occurred repeatedly in independent Plasmodium falciparum lineages exposed to the antimalarial drug atovaquone-proguanil (AP). We analyzed the history of 7 AP resistance alleles from clinical isolates by sequencing the mitochondrial (mt) genome that encodes the pfcytb gene and found that a distinct mt haplotype was associated with each AP resistance allele. By comparing mt sequences and microsatellite genotypes of the isolates both before treatment initiation and at the day of failure for each uncured patient, we observed that the AP resistance alleles occurred and spread within the patients. These data demonstrate that identical AP resistance alleles have multiple independent origins and provide an example of parallel evolution driven by drug treatment selection in P. falciparum.
- Published
- 2007
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