Rapid identification of genes controlling virulence and immunity in malaria parasites

Anderson, T. J.C. et al. (2017) Rapid identification of genes controlling virulence and immunity in malaria parasites. PLoS Pathogens, 13(7), e1006447. (doi: 10.1371/journal.ppat.1006447) (PMID:28704525) (PMCID:PMC5507557)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Anderson, T. J.C., Abkallo, H. M., Martinelli, A., Inoue, M., Ramaprasad, A., Xangsayarath, P., Gitaka, J., Tang, J., Yahata, K., Zoungrana, A., Mitaka, H., Acharjee, A., Datta, P. P., Hunt, P., Carter, R., Kaneko, O., Mustonen, V., Illingworth, C. J. R., Pain, A., and Culleton, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 12 July 2017
• Copyright Holders: Copyright © 2017 Abkallo et al.
• First Published: First published in PLoS Pathogens 13(7): e1006447
• Publisher Policy: Reproduced under a Creative Commons License