Limited Polymorphism of the Kelch Propeller Domain in Plasmodium malariae and P. ovale Isolates from Thailand

<jats:title>ABSTRACT</jats:title><jats:p>Artemisinin resistance in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium falciparum</jats:named-content>, the agent of severe malaria, is currently a major obstacle to malaria control in Southeast Asia. A gene named “<jats:italic>kelch13</jats:italic>” has been associated with artemisinin resistance in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>. The orthologue of the<jats:italic>kelch</jats:italic>gene in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>was identified and a small number of mutations were found in previous studies. The<jats:italic>kelch</jats:italic>orthologues in the other two human malaria parasites,<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. malariae</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale</jats:named-content>, have not yet been studied. Therefore, in this study, the orthologous<jats:italic>kelch</jats:italic>genes of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. malariae</jats:named-content>,<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale wallikeri</jats:named-content>, and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale curtisi</jats:named-content>were isolated and analyzed for the first time. The homologies of the<jats:italic>kelch</jats:italic>genes of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. malariae</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale</jats:named-content>were 84.8% and 82.7%, respectively, compared to the gene in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>.<jats:italic>kelch</jats:italic>polymorphisms were studied in 13<jats:italic>P. malariae</jats:italic>and 5<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale</jats:named-content>isolates from Thailand. There were 2 nonsynonymous mutations found in these samples. One mutation was P533L, which was found in 1 of 13<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. malariae</jats:named-content>isolates, and the other was K137R, found in 1 isolate of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale wallikeri</jats:named-content>(<jats:italic>n</jats:italic>= 4). This result needs to be considered in the context of widespread artemisinin used within the region; their functional consequences for artemisinin sensitivity in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. malariae</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. ovale</jats:named-content>will need to be elucidated.</jats:p>