Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia
Abstract Background Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone ® ) and inhibits the cytochrome bc 1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-b...
| Published in: | Malaria Journal |
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| Main Authors: | , , , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
BMC
2006
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| Subjects: | |
| Online Access: | https://doi.org/10.1186/1475-2875-5-112 https://doaj.org/article/9f889f8a9a894f338ac06ab46124c683 |
| Summary: | Abstract Background Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone ® ) and inhibits the cytochrome bc 1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b , thus resulting in drug resistance. Methods The prevalence of cytochrome b point mutations possibly conferring atovaquone resistance in Plasmodium falciparum isolates in atovaquone treatment-naïve patient cohorts from Lambaréné, Gabon and from South Western Ethiopia was assessed. Results Four/40 (10%) mutant types (four different single polymorphisms, one leading to an amino acid change from M to I in a single case) in Gabonese isolates, but all 141/141 isolates were wild type in Ethiopia were found. Conclusion In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare. |
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