PMRT1, a <i>Plasmodium</i> -Specific Parasite Plasma Membrane Transporter, Is Essential for Asexual and Sexual Blood Stage Development
Jan Stephan Wichers-Misterek, Paolo Mesén-Ramírez, Gwendolin Fuchs, Jing Yu-Strzelczyk, Jan Stäcker, Heidrun von Thien, Arne Alder, Isabelle G. Henshall, Benjamin Liffner, Georg Nagel, Christian Löw, Danny W. Wilson, Tobias Spielmann, Shiqiang Gao, Tim‐Wolf Gilberger, Anna Bachmann, Jan Strauss
Abstract
Plasmodium falciparum-infected erythrocytes possess multiple compartments with designated membranes. Transporter proteins embedded in these membranes not only facilitate movement of nutrients, metabolites, and other molecules between these compartments, but also are common therapeutic targets and can confer antimalarial drug resistance. Orphan membrane transporters in P. falciparum without sequence homology to transporters in other evolutionary lineages and divergent from host transporters may constitute attractive targets for novel intervention approaches. Here, we localized six of these putative transporters at different subcellular compartments and probed their importance during asexual parasite growth by using reverse genetic approaches. In total, only two candidates turned out to be dispensable for the parasite, highlighting four candidates as putative targets for therapeutic interventions. This study reveals the importance of several orphan transporters to blood stage P. falciparum development.