Rapid identification of genes controlling virulence and immunity in malaria parasites.

oleh: 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

Format: Article
Diterbitkan: Public Library of Science (PLoS) 2017-07-01

Deskripsi

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.