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CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection
- Source :
- PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2018, 14 (3), pp.e1006898. ⟨10.1371/journal.ppat.1006898⟩, PLoS Pathogens, Vol 14, Iss 3, p e1006898 (2018), PLoS Pathogens, 2018, 14 (3), pp.e1006898. ⟨10.1371/journal.ppat.1006898⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
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.<br />Author summary The causative agent of malaria, Plasmodium, has to complete a complex infection cycle in the Anopheles gambiae mosquito vector in order to reach the salivary gland from where it can be transmitted to a human host. The parasite’s development in the mosquito relies on numerous host factors (agonists), and their inhibition or inactivation can thereby result in suppression of infection and consequently malaria transmission. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities to delete (inactivate) Plasmodium agonists to better understand their function and for blocking malaria transmission. Here we have established a modified CRISPR/Cas9 genome editing technique for malaria vector A. gambiae mosquitoes. Through this approach we have inactivated the fibrinogen-related protein 1 (FREP1) gene, via CRISPR/Cas9 genome editing, and the impact of this manipulation on the mosquito’s susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants showed a profound suppression of infection with both human and rodent malaria parasites, while it also resulted in fitness costs: a significantly lower blood-feeding propensity, fecundity and egg hatching rate, and a retarded larval development and pupation time, and reduced longevity after a blood meal.
- Subjects :
- 0301 basic medicine
Plasmodium
Physiology
Anopheles gambiae
Disease Vectors
Mosquitoes
Synthetic Genome Editing
Genome Engineering
Gene Knockout Techniques
Mice
0302 clinical medicine
Medicine and Health Sciences
CRISPR
Malaria, Falciparum
lcsh:QH301-705.5
Protozoans
Anopheles
Malarial Parasites
Crispr
Eukaryota
3. Good health
Body Fluids
Insects
Infectious Diseases
Blood
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Sporozoites
Engineering and Technology
Insect Proteins
Synthetic Biology
Anatomy
Research Article
Biotechnology
lcsh:Immunologic diseases. Allergy
Arthropoda
Immunology
Plasmodium falciparum
Bioengineering
Biology
Research and Analysis Methods
Microbiology
Gene Knockout
03 medical and health sciences
Virology
Parasite Groups
parasitic diseases
Genetics
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Parasitic Diseases
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Molecular Biology Techniques
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Molecular Biology
Gene knockout
Cas9
Organisms
Oocysts
Biology and Life Sciences
Synthetic Genomics
biology.organism_classification
medicine.disease
Tropical Diseases
Invertebrates
Parasitic Protozoans
Insect Vectors
Malaria
Species Interactions
030104 developmental biology
lcsh:Biology (General)
Synthetic Bioengineering
Artificial Genetic Recombination
Parasitology
CRISPR-Cas Systems
lcsh:RC581-607
Apicomplexa
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2018, 14 (3), pp.e1006898. ⟨10.1371/journal.ppat.1006898⟩, PLoS Pathogens, Vol 14, Iss 3, p e1006898 (2018), PLoS Pathogens, 2018, 14 (3), pp.e1006898. ⟨10.1371/journal.ppat.1006898⟩
- Accession number :
- edsair.doi.dedup.....a3946edbb7a9720f1292caeda4a4a7d2