Complexin in ivermectin resistance in body lice Amanzougaghene, N. Fenollar, F. Nappez, C. Ben-Amara, A. Decloquement, P. Azza, S. Bechah, Y. Chabriere, E. Raoult, D. /Mediannikov, Oleg 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. 2018 text https://www.documentation.ird.fr/hor/fdi:010073981 fdi:010073981 Amanzougaghene N., Fenollar F., Nappez C., Ben-Amara A., Decloquement P., Azza S., Bechah Y., Chabriere E., Raoult D., Mediannikov Oleg. Complexin in ivermectin resistance in body lice. 2018, 14 (8), e1007569 [18 p.] EN