Amanzougaghene N. auteur aut IRD Fenollar F. auteur aut IRD Nappez C. auteur aut IRD Ben-Amara A. auteur aut IRD Decloquement P. auteur aut IRD Azza S. auteur aut IRD Bechah Y. auteur aut IRD Chabriere E. auteur aut IRD Raoult D. auteur aut IRD Mediannikov Oleg auteur aut IRD text journalArticle eng text/pdf reformatted digital access 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. specialized 052 050 14 8 e1007569 [18 p.] 2018 1553-7404 https://www.documentation.ird.fr/hor/fdi:010073981 10.1371/journal.pgen.1007569 1553-7404 [F B010073981] https://www.documentation.ird.fr/hor/fdi:010073981 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers18-09/010073981.pdf IRD - Base Horizon / Pleins textes 2018-10-03 2023-07-11 fdi:010073981 fre