Abstract
Background: Malaria control heavily relies on insecticide-based interventions against mosquito vectors. However, the increasing spread of insecticide resistance is a major threat. The extent to which such resistance, notably metabolic resistance, interferes with the development of the Plasmodium parasite and its impact on overall malaria transmission remains poorly characterized. Here, we investigated whether glutathione S-transferase-based resistance could influence Plasmodium falciparum development in Anopheles funestus. Methods: Anopheles funestus females were infected with P. falciparum gametocytes and midguts were dissected at day 7 post infection for detection/quantification of oocysts. Infection parameters were compared between individual with different L119F-GSTe2 genotypes, and the polymorphism of the GSTe2 gene was analyzed in infected and uninfected mosquito groups. Results: Overall, 403 mosquitoes were dissected and genotyped. The frequency of the L119F-GSTe2 resistance allele was significantly higher in non-infected (55.88%) compared to infected (40.99%) mosquitoes (Fisher's exact test, P<0.0001). Prevalence of infection was significantly higher in heterozygous and homozygous susceptible genotypes (P<0.001). However, homozygous resistant and heterozygous mosquitoes exhibited significantly higher infection intensity (P<0.01). No association was observed between the GSTe2 polymorphism and the infection status of mosquitoes. Conclusion: Altogether, these results suggest that GSTe2-based metabolic resistance may affect the vectorial competence of resistant An. funestus mosquitoes to P. falciparum infection, by increasing its permissiveness to Plasmodium infection.
Highlights
Better to indicate the specific species in the An. gambaie sl where selection for resistance has been reported
Taking advantage of availability of this new DNA-based GSTe2 marker, we investigated the impact of a glutathione S-transferase (GST)-mediated metabolic resistance on the vector competence of the major malaria vector An. funestus
We showed that the L119F-GSTe2 mutation conferring pyrethroid/DDT resistance could influence P. falciparum infection in field populations of this vector
Summary
Better to indicate the specific species in the An. gambaie sl where selection for resistance has been reported This is a species complex and not sure such data exists for all members in this group. Reviewer's comment 3: Better to indicate the specific species in the An. gambaie sl where selection for resistance has been reported The authors found lower Plasmodium infection rate in the mosquitoes expressing resistance allele but higher oocyst intensity in this genotype. I am not convinced about the authors being emphatic that GSTe2-based metabolic resistance increases the mosquito permissiveness to Plasmodium infection as stated in the conclusion.
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