Rapid identification of genes controlling virulence and immunity in malaria parasites

Hussein M. Abkallo, Axel Martinelli, Megumi Inoue, Abhinay Ramaprasad, Phonepadith Xangsayarath, Jesse Gitaka, Jianxia Tang, Kazuhide Yahata, Augustin Zoungrana, Hayato Mitaka, Arita Acharjee, Partha P. Datta, Paul Hunt, Richard Carter, Osamu Kaneko, Ville Mustonen, Christopher J. R. Illingworth, Arnab Pain, Richard Culleton

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Identifying 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.
Original languageEnglish (US)
Pages (from-to)e1006447
JournalPLOS Pathogens
Volume13
Issue number7
DOIs
StatePublished - Jul 12 2017

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