Complexin in ivermectin resistance in body lice

Ivermectin has emerged as very promising pediculicide, particularly in cases of resistance to commonly used pediculicides. Recently, however, the first field-evolved ivermectin-resis- tance in lice was reported. To gain insight into the mechanisms underlying ivermectin-resis- tance, 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 resis- tance 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 evi- dence that links complexin to insecticide resistance.

December 2022 - This article has been identified as one of a series of submissions for which we have concerns about the reported research ethics approval information and the article’s adherence to PLOS research ethics policies. PLOS will be investigating these concerns in accordance with COPE guidance and journal policies. Meanwhile, the PLOS Genetics Editors issue this Expression of Concern. See https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1... or https://phthiraptera.myspecies.info/node/96441