Rapid identification of genes controlling virulence and immunity in malaria parasites
AuthorsAbkallo, Hussein M.
Datta, Partha P.
Illingworth, Christopher J. R.
KAUST Grant NumberBAS/1/1020-01-01
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AbstractIdentifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.
CitationAbkallo HM, Martinelli A, Inoue M, Ramaprasad A, Xangsayarath P, et al. (2017) Rapid identification of genes controlling virulence and immunity in malaria parasites. PLOS Pathogens 13: e1006447. Available: http://dx.doi.org/10.1371/journal.ppat.1006447.
SponsorsThis work was supported by the JSPS (project numbers Nos. JP25870525, JP24255009 and JP16K21233) (to RCu), A Royal Society Bilateral Grant for Co-operative Research (to RCa and RCu) and a Sasakawa Foundation Butterfield Award (to RCu), faculty baseline fund (BAS/1/1020-01-01) from the King Abdullah University of Science and Technology (KAUST) to AP, and Grants-in-Aid for Scientific Research on Innovative Areas JR23117008 (to OK). CJRI was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (101239/Z/13/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PublisherPublic Library of Science (PLoS)
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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