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PLoS Pathog. 2017 Jul 12;13(7):e1006447. doi: 10.1371/journal.ppat.1006447. eCollection 2017 Jul.

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

Author information

1
Malaria Unit, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
2
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
3
Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
4
Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
5
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
6
Department of Protozooolgy, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
7
Centre for Malaria Elimination, School of Medicine, Mount Kenya University, Thika, Kenya.
8
Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Jiangsu, China.
9
Indian Institute of Science Education and Research Kolkata, Mohanpur - 741 246, West Bengal, India.
10
Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
11
Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
12
Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, United Kingdom.

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.

PMID:
28704525
PMCID:
PMC5507557
DOI:
10.1371/journal.ppat.1006447
[Indexed for MEDLINE]
Free PMC Article

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