Sequence analysis of Plasmodium falciparum SERCA-type pfATPase6 in field isolates collected along Thai-Cambodian border

Abstract

Background: Polymorphisms in the P. falciparum gene for ATPase6 (pfATPase6) have been proposed as markers for artemisinin resistance, though the precise artemisinin binding pocket has not yet been comprehensively investigated in cases of treatment failure from along the Thai-Cambodian border. Objective: To investigate the specific regions of pfATPase6 in adequate clinical and parasitological response and treatment failures from Thai-Cambodian border. Methods: We examined polymorphisms in pfATPase6 by sequence analysis in parasites collected from 164 patients with uncomplicated malaria showing variable clinical phenotypes (13 cases of treatment failure and 151adequate clinical and parasitological response) from adjacent areas on either side of the Thai-Cambodian border during the period 2005-2007. We investigated potential correlations between putative binding pocketpolymorphisms with clinical response. Results: The majority of DNA sequences coding for the proposed artesunate binding pocket (M3, M5, and M7 helices) and the regions around Ser769 were conserved in parasite populations collected from patients in both study sites, regardless of clinical outcome. Conclusions: The previously proposed areas of pfATPase6 did not appear to vary based on clinical outcome in a large number of patients from Southeast Asia, suggesting these regions are unlikely to be useful asmolecular markers of resistance in clinical specimens from the Southeast Asian region. Keywords: PfATPase6, pfATP6, plasmodium falciparum, SERCA