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About the Authors:
Yuemei Dong
Roles Formal analysis, Investigation, Methodology, Validation, Writing - original draft
Affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Malaria Research Institute, Johns Hopkins University, Baltimore, Maryland, United States of America
Maria L. Simões
Roles Investigation, Methodology
Affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Malaria Research Institute, Johns Hopkins University, Baltimore, Maryland, United States of America
Eric Marois
Roles Conceptualization, Investigation, Methodology, Supervision, Writing - review & editing
Affiliation: Inserm, CNRS, Université de Strasbourg, Strasbourg, France
ORCID http://orcid.org/0000-0003-4147-3747
George Dimopoulos
Roles Conceptualization, Project administration, Supervision, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Malaria Research Institute, Johns Hopkins University, Baltimore, Maryland, United States of America
ORCID http://orcid.org/0000-0001-6755-8111Abstract
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.
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...