Abstract
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.
Highlights
Sucking lice (Anoplura) are obligate blood-feeding ectoparasites of eutherian mammals [1]
Ivermectin-selected resistant body lice, a complexin, a neuronal protein that plays a key role in regulating neurotransmitter release, was shown to be the most significantly downexpressed protein in ivermectin-resistant lice
Its down-expression by RNA-interference in susceptible lice induced resistance to ivermectin, providing evidence that complexin plays a significant role in regulating ivermectin resistance
Summary
Sucking lice (Anoplura) are obligate blood-feeding ectoparasites of eutherian mammals [1]. Studies have shown that experimentally infected head lice are capable of acquiring, maintaining and transmitting R. prowazekii and B. quintana, demonstrating that these lice have the potential to be a vector of pathogen under optimal epidemiological conditions [9,10]. This fact may pose a very substantial threat to humanity, as such infestations are not controlled in any country, including developed countries, despite repeated efforts to eradicate them [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
