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An alternative dogma on reduced artemisinin susceptibility: A new shadow from east to west

2019; National Academy of Sciences; Volume: 116; Issue: 26 Linguagem: Inglês

10.1073/pnas.1907142116

1091-6490

Thirumalaisamy P. Velavan, David Nderu, Tsiri Agbenyega, Francine Ntoumi, Peter G. Kremsner,

Trypanosoma species research and implications

In PNAS, Demas et al. (1) show, by long-term in vitro selection using culture-adapted Plasmodium falciparum isolates from Senegal, that the gene encoding the actin-binding protein P. falciparum coronin (pfcoronin) and its genetic variants (G50E, R100K, and E107V) can reduce the susceptibility of the parasite to the active metabolite of the fast-acting antimalarial drug artemisinin, dihydroartemisinin (DHA).Resistance to artemisinins is a global threat in malaria control and elimination efforts (2).Artemisinin resistance, first reported in Southeast Asia and still extremely rare, was associated with the P. falciparum PfKelch13-propeller domain (kelch13 mutations: Y493H, R539T, I543T, and C580Y) (3).PfCoronin, which is structurally similar to Kelch13, is believed to interact with F-actin via its N-terminal propeller domain and to mediate actin organization and motility in merozoites and sporozoites (4, 5).The worldwide map of the occurrence of kelch13, however, indicates absence of the Asian artemisininresistance alleles in Africa (6-8).So far, it is not clear whether the pfcoronin variants G50E, R100K, and E107V occur in natural P. falciparum populations-in particular, in clinical isolates from Africa.We looked at a total of 353 P. falciparum patient isolates that were earlier characterized for the absence of kelch13 gene mutations (7-10) from 4 African countries to verify whether these isolates carry the pfcoronin mutations G50E, R100K, and E107V, which were described by Demas et al. (1) to be associated with reduced susceptibility to DHA.A total of 297 samples