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© Research
Publication : Scientific reports

The voltage-gated sodium channel, para, limits Anopheles coluzzii vector competence in a microbiota dependent manner.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Scientific reports - 01 Sep 2023

Nardini L, Brito-Fravallo E, Campagne P, Pain A, Genève C, Vernick KD, Mitri C

Link to Pubmed [PMID] – 37666840

Link to HAL – pasteur-04201637

Link to DOI – 10.1038/s41598-023-40432-x

Sci Rep 2023 Sep; 13(1): 14572

The voltage-gated sodium channel, para, is a target of DDT and pyrethroid class insecticides. Single nucleotide mutations in para, called knockdown resistant or kdr, which contribute to resistance against DDT and pyrethroid insecticides, have been correlated with increased susceptibility of Anopheles to the human malaria parasite Plasmodium falciparum. However, a direct role of para activity on Plasmodium infection has not yet been established. Here, using RNA-mediated silencing, we provide in vivo direct evidence for the requirement of wild-type (wt) para function for insecticide activity of deltamethrin. Depletion of wt para, which is susceptible to insecticide, causes deltamethrin tolerance, indicating that insecticide-resistant kdr alleles are likely phenocopies of loss of para function. We then show that normal para activity in An. coluzzii limits Plasmodium infection prevalence for both P. falciparum and P. berghei. A transcriptomic analysis revealed that para activity does not modulate the expression of immune genes. However, loss of para function led to enteric dysbiosis with a significant increase in the total bacterial abundance, and we show that para function limiting Plasmodium infection is microbiota dependent. In the context of the bidirectional “enteric microbiota-brain” axis studied in mammals, these results pave the way for studying whether the activity of the nervous system could control Anopheles vector competence.