Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets
Authors:January Weiner 3rd1 and Taco W.A. Kooij2
doi: 10.15698/mic2016.10.534
Volume 3, pp. 511 to 521, published 30/08/2016.
1 Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
2 Department of Medical Microbiology & Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Keywords:
drug target, experimental genetics, malaria parasite, membrane transport protein, orthology, phylogeny, Plasmodium.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no existing conflicts of interest.
Please cite this article as:
January Weiner 3rd and Taco W.A. Kooij (2016). Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets. Microbial Cell 3(10): 511-521. doi: 10.15698/mic2016.10.534
© 2016 Weiner and Kooij. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. To survive within host cells, the parasites need to acquire nutrients and dispose of waste products across multiple membranes. Additionally, like all eukaryotes, they must redistribute ions and organic molecules between their various internal membrane bound compartments. Membrane transport proteins mediate all of these processes and are considered important mediators of drug resistance as well as drug targets in their own right. Recently, using advanced experimental genetic approaches and streamlined life cycle profiling, we generated a large collection of Plasmodium berghei gene deletion mutants and assigned essential gene functions, highlighting potential targets for prophylactic, therapeutic, and transmission-blocking anti-malarial drugs. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites. Furthermore, we discuss the phylogeny of selected potential drug targets identified in our functional screen. We extensively discuss the results in the context of the functional assignments obtained using gene targeting available to date.