%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Amanzougaghene, N.
%A Fenollar, F.
%A Nappez, C.
%A Ben-Amara, A.
%A Decloquement, P.
%A Azza, S.
%A Bechah, Y.
%A Chabriere, E.
%A Raoult, D.
%A Mediannikov, Oleg
%T Complexin in ivermectin resistance in body lice
%D 2018
%L fdi:010073981
%G ENG
%J PLoS Genetics
%@ 1553-7404
%M ISI:000443389100027
%N 8
%P e1007569 [18 ]
%R 10.1371/journal.pgen.1007569
%U https://www.documentation.ird.fr/hor/fdi:010073981
%> https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers18-09/010073981.pdf
%V 14
%W Horizon (IRD)
%X Ivermectin has emerged as very promising pediculicide, particularly in cases of resistance to commonly used pediculicides. Recently, however, the first field-evolved ivermectin-resistance in lice was reported. To gain insight into the mechanisms underlying ivermectin-resistance, we both looked for mutations in the ivermectin-target site (GluCl) and searched the entire proteome for potential new loci involved in resistance from laboratory susceptible and ivermectin-selected resistant body lice. Polymorphism analysis of cDNA GluCl showed no non-silent mutations. Proteomic analysis identified 22 differentially regulated proteins, of which 13 were upregulated and 9 were downregulated in the resistant strain. We evaluated the correlation between mRNA and protein levels by qRT-PCR and found that the trend in transcriptional variation was consistent with the proteomic changes. Among differentially expressed proteins, a complexin i.e. a neuronal protein which plays a key role in regulating neurotransmitter release, was shown to be the most significantly down-expressed in the ivermectin-resistant lice. Moreover, DNA-mutation analysis revealed that some complexin transcripts from resistant lice gained a premature stop codon, suggesting that this down-expression might be due, in part, to secondary effects of a nonsense mutation inside the gene. We further confirmed the association between complexin and ivermectin-resistance by RNA-interfering and found that knocking down the complexin expression induces resistance to ivermectin in susceptible lice. Our results provide evidence that complexin plays a significant role in regulating ivermectin resistance in body lice and represents the first evidence that links complexin to insecticide resistance.
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