Rapid identification of genes controlling virulence and immunity in malaria parasites
Type
ArticleAuthors
Abkallo, Hussein M.Martinelli, Axel
Inoue, Megumi
Ramaprasad, Abhinay

Xangsayarath, Phonepadith
Gitaka, Jesse
Tang, Jianxia
Yahata, Kazuhide
Zoungrana, Augustin
Mitaka, Hayato
Acharjee, Arita
Datta, Partha P.
Hunt, Paul
Carter, Richard
Kaneko, Osamu
Mustonen, Ville
Illingworth, Christopher J. R.
Pain, Arnab

Culleton, Richard

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
KAUST Grant Number
BAS/1/1020-01-01Date
2017-07-12Permanent link to this record
http://hdl.handle.net/10754/625229
Metadata
Show full item recordAbstract
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.Citation
Abkallo 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.Sponsors
This 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.Publisher
Public Library of Science (PLoS)Journal
PLOS PathogensPubMed ID
28704525ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1006447
Scopus Count
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