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

Yuemei Dong, Maria L. Simões, Eric Marois, George Dimopoulos

Research output: Contribution to journalArticle

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 (US)
Article numbere1006898
JournalPLoS Pathogens
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2018

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Clustered Regularly Interspaced Short Palindromic Repeats
Anopheles gambiae
Gene Knockout Techniques
Parasitic Diseases
Culicidae
Fibrinogen
Malaria
Plasmodium
Proteins
Sporozoites
Anopheles
Oocysts
Gene Deletion
Ovum
Fertility
Meals
Rodentia
Parasites
Costs and Cost Analysis
Infection

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection. / Dong, Yuemei; Simões, Maria L.; Marois, Eric; Dimopoulos, George.

In: PLoS Pathogens, Vol. 14, No. 3, e1006898, 01.03.2018.

Research output: Contribution to journalArticle

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