The voltage-gated sodium channel, para, limits Anopheles coluzzii vector competence in a microbiota dependent manner.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 09 2023
04 09 2023
Historique:
received:
21
03
2023
accepted:
10
08
2023
medline:
6
9
2023
pubmed:
5
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37666840
doi: 10.1038/s41598-023-40432-x
pii: 10.1038/s41598-023-40432-x
pmc: PMC10477260
doi:
Substances chimiques
decamethrin
2JTS8R821G
DDT
CIW5S16655
Insecticides
0
Voltage-Gated Sodium Channels
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14572Subventions
Organisme : NIAID NIH HHS
ID : R01 AI145999
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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