CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection

Yuemei Dong, Maria Luisa Simões, Eric Marois, George Dimopoulos

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    Abstract

    Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito's susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants developed into adult mosquitoes that showed profound suppression of infection with both human and rodent malaria parasites at the oocyst and sporozoite stages. FREP1 inactivation, however, resulted in fitness costs including a significantly lower blood-feeding propensity, fecundity and egg hatching rate, a retarded pupation time, and reduced longevity after a blood meal.

    Original languageEnglish
    Article numbere1006898
    JournalPLoS Pathogens
    Volume14
    Issue number3
    ISSN1553-7366
    DOIs
    Publication statusPublished - 2018

    Keywords

    • Animals
    • Anopheles/immunology
    • CRISPR-Cas Systems
    • Gene Knockout Techniques
    • Humans
    • Insect Proteins/antagonists & inhibitors
    • Malaria, Falciparum/immunology
    • Mice
    • Oocysts/immunology
    • Plasmodium falciparum/isolation & purification
    • Sporozoites/immunology

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