Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum
Abstract Artemisinins are the current mainstay of malaria chemotherapy. Their exact mode of action is an ongoing matter of debate, and several factors have recently been reported to affect an early stage of artemisinin resistance of the most important human malaria parasite Plasmodium falciparum. He...
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doaj-80aec3c117b048aab371a5c43075b7a32020-12-08T00:02:53ZengNature Publishing GroupScientific Reports2045-23222017-06-017111110.1038/s41598-017-04277-5Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparumCarine F. Djuika0Verena Staudacher1Cecilia P. Sanchez2Michael Lanzer3Marcel Deponte4Department of Parasitology, Ruprecht-Karls UniversityDepartment of Parasitology, Ruprecht-Karls UniversityDepartment of Parasitology, Ruprecht-Karls UniversityDepartment of Parasitology, Ruprecht-Karls UniversityDepartment of Parasitology, Ruprecht-Karls UniversityAbstract Artemisinins are the current mainstay of malaria chemotherapy. Their exact mode of action is an ongoing matter of debate, and several factors have recently been reported to affect an early stage of artemisinin resistance of the most important human malaria parasite Plasmodium falciparum. Here, we identified a locus on chromosome 7 that affects the artemisinin susceptibility of P. falciparum in a quantitative trait locus analysis of a genetic cross between strains 7G8 and GB4. This locus includes the peroxiredoxin gene PFAOP. However, steady-state kinetic data with recombinant PfAOP do not support a direct interaction between this peroxidase and the endoperoxide artemisinin. Furthermore, neither the overexpression nor the deletion of the encoding gene affected the IC50 values for artemisinin or the oxidants diamide and tert-butyl hydroperoxide. Thus, PfAOP is dispensable for blood stage parasite survival, and the correlation between the artemisinin susceptibility and chromosome 7 is probably based on another gene within the identified locus.https://doi.org/10.1038/s41598-017-04277-5 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carine F. Djuika Verena Staudacher Cecilia P. Sanchez Michael Lanzer Marcel Deponte |
spellingShingle |
Carine F. Djuika Verena Staudacher Cecilia P. Sanchez Michael Lanzer Marcel Deponte Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum Scientific Reports |
author_facet |
Carine F. Djuika Verena Staudacher Cecilia P. Sanchez Michael Lanzer Marcel Deponte |
author_sort |
Carine F. Djuika |
title |
Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum |
title_short |
Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum |
title_full |
Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum |
title_fullStr |
Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum |
title_full_unstemmed |
Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum |
title_sort |
knockout of the peroxiredoxin 5 homologue pfaop does not affect the artemisinin susceptibility of plasmodium falciparum |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-06-01 |
description |
Abstract Artemisinins are the current mainstay of malaria chemotherapy. Their exact mode of action is an ongoing matter of debate, and several factors have recently been reported to affect an early stage of artemisinin resistance of the most important human malaria parasite Plasmodium falciparum. Here, we identified a locus on chromosome 7 that affects the artemisinin susceptibility of P. falciparum in a quantitative trait locus analysis of a genetic cross between strains 7G8 and GB4. This locus includes the peroxiredoxin gene PFAOP. However, steady-state kinetic data with recombinant PfAOP do not support a direct interaction between this peroxidase and the endoperoxide artemisinin. Furthermore, neither the overexpression nor the deletion of the encoding gene affected the IC50 values for artemisinin or the oxidants diamide and tert-butyl hydroperoxide. Thus, PfAOP is dispensable for blood stage parasite survival, and the correlation between the artemisinin susceptibility and chromosome 7 is probably based on another gene within the identified locus. |
url |
https://doi.org/10.1038/s41598-017-04277-5 |
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