1. Disparate selection of mutations in the dihydrofolate reductase gene (dhfr) of Plasmodium ovale curtisi and P. o. wallikeri in Africa.
- Author
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Chen, Jing, Ma, Xiaoqin, Tang, Jianxia, Xu, Sui, Gu, Yaping, Tang, Feng, Cao, Yuanyuan, Wang, Weiming, Zhou, Huayun, Zhang, Jiayao, Yu, Xinyu, Zhu, Guoding, Zhu, Meng, Zhang, Qingfeng, Culleton, Richard, Liu, Yaobao, and Cao, Jun
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TETRAHYDROFOLATE dehydrogenase ,PLASMODIUM ,MICROSATELLITE repeats ,PLASMODIUM vivax ,GENETIC variation ,MELIOIDOSIS ,TREMATODA - Abstract
Plasmodium ovale curtisi and P. ovale wallikeri are both endemic in sub-Saharan Africa, the Middle East and Southeast Asia. Molecular surveillance data for drug resistance in P. ovale spp. is limited at present. We analysed polymorphisms in the podhfr, pocrt and pocytb genes of P. ovale spp. in 147 samples collected from travelers returning to China from Africa. Two podhfr mutations, S58R and S113N/T were detected in P. ovale curtisi with high/moderate frequencies of 52.17% and 17.39%, respectively. Evidence of positive selection (d
N /dS = 2.41) was found for podhfr in P. ovale curtisi and decreased diversity (He ) of microsatellite markers flanking the mutant alleles suggests that selective sweeps have occurred for both. Mutations E34G (1.50%) and L43V (1.50%) in pocrt of P. ovale curtisi, and E34G (3.70%), I102M (1.80%) and V111F (1.80%) of P. ovale wallikeri were found at low frequencies. Mutations R66K (6.20%), R75K (11.63%) and R95K (3.88%) of pocytb were found in both P. ovale curtisi and P. ovale wallikeri. These results suggest that the podhfr gene of P. ovale curtisi may be subject to drug selection in Africa, warranting further attention. We observed significant differences in the prevalence and distribution of podhfr mutations between the two P. ovale species, suggestive of fundamental biological differences between them. Author summary: The importance of the hitherto neglected malaria parasites Plasmodium ovale curtisi, Plasmodium ovale wallikeri and Plasmodium malariae is now becoming apparent. It is clear that these species are prevalent in Africa at much higher rates than previously thought, and that they are responsible for a significant amount of malaria-related morbidity. There is very little currently known about the epidemiology of these parasites, despite their importance. Of particular importance is understanding whether these parasites undergo selection for drug resistance in similar ways as Plasmodium falciparum and Plasmodium vivax. The fact that little is known regarding the molecular epidemiology of these parasites is due to difficulties in identifying them in the field, the fact that they are often present at low parasite densities in the blood, are often masked by co-infection with P. falciparum, and that there is no in vitro culture system available for them. We were able to utilise a unique and priceless resource–P. ovale spp. samples, mostly in mono-infections, from non-immune Chinese travellers to Africa–to sequence orthologues of several genes known to be linked to drug resistance in other malaria parasite species. This resource enabled us to sample a number of parasites from a widespread geographical area; something that has never before been possible. Through sequencing of the orthologues of several genes known to be linked to drug resistance in other malaria parasite species, high frequencies of S58R and S113N/T mutations were observed in podhfr in P. ovale curtisi isolates from Africa. Furthermore, by surveying the genetic diversity around these loci using microsatellite markers, we were able to show that the podhfr gene of African P. ovale curtisi has undergone selection for particular mutations, probably due to drug pressure, and this warrants further attention. [ABSTRACT FROM AUTHOR]- Published
- 2022
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