PLOS ONE
PLOS ONE
4 years ago

Rapid identification of genes controlling virulence and immunity in malaria parasites

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

by 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

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.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.ppat.1006447

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