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Conference Agenda

Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).

Daily Overview

Session

CP11: Cells, Molecules & Genes 2 - 10 min talks
Location: Lecture Theatre 1
Session Chair: Ellis Joch, Griffith University
Session Chair: Wisam Dawood, Griffith University

Presentation 2

Two novel apicoplast transporters with different, crucial roles in malaria parasite life cycle

Laura J. Akkerman¹, Roos Weeda¹, Pingping Zhu², Robert S. Jansen², Eric Beitz³, Laura E. de Vries^1,4, Taco W.A. Kooij^1,4

1: Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands; 2: Microbiology Department, Radboud University, Nijmegen, the Netherlands; 3: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany; 4: Contributed equally

Malaria parasites depend on the apicoplast, an intriguing organelle of algal origin, for survival throughout the life cycle. Transport of metabolites across the apicoplast membranes is poorly understood, and only 11 transporter proteins have been confirmed to localize to the organelle to date. We report apicoplast localization of two previously uncharacterized transporters in Plasmodium falciparum. Knockdown of apicoplast transporter 1 (at1) resulted in death of asexual blood-stage parasites. Knockout of at1 in PfMev parasites, which have a metabolic apicoplast bypass, resulted in disruption of apicoplast morphology and loss of the organellar genome, suggesting that AT1 is involved in apicoplast housekeeping. Knockout of apicoplast transporter 2 (at2) did not affect asexual blood-stage parasites, nor gametocyte and gamete formation. In the mosquito, however, oocyst size was significantly decreased and no sporozoites were observed in salivary glands up until day 21, phenocopying knockouts of fatty acid metabolism. Metabolomics, drug assays, transport assays in yeast, and protein modeling provided further information on candidate substrates for both transporters. Taken together, we identified two novel apicoplast transporters, with AT1 being essential for asexual blood stages by supporting apicoplast housekeeping, and AT2 being important for parasite growth in mosquitoes, possibly by facilitating fatty acid metabolism.