Rapid identification of genes controlling virulence and immunity in malaria parasites

• Published in: PLoS pathogens 2017-07, Vol.13 (7), p.e1006447
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Antigens; Antigens, Protozoan - genetics; Antigens, Protozoan - metabolism; Binding; Bioinformatics; Biology and Life Sciences; Blood; Blood cells; Collaboration; Engineering; Environmental science; Erythrocytes; Erythrocytes - parasitology; Gene polymorphism; Genes; Genetic aspects; Genomes; Growth rate; Host-Parasite Interactions; Humans; Identification and classification; Immunity; Immunology; Infections; Laboratories; Malaria; Malaria - genetics; Malaria - immunology; Malaria - parasitology; Medicine; Medicine and Health Sciences; Merozoite surface protein 1; Merozoite Surface Protein 1 - genetics; Merozoite Surface Protein 1 - metabolism; Neural networks; Pain; Parasites; Parasitic diseases; Pathology; Phenotypes; Plasmodium yoelii - genetics; Plasmodium yoelii - growth & development; Plasmodium yoelii - metabolism; Plasmodium yoelii - pathogenicity; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Research and Analysis Methods; Science education; Signal processing; Single-nucleotide polymorphism; Vector-borne diseases; Virulence; Virulence (Microbiology); Zoonoses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006447

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.