Project description:Human lice are the only hematophagous ectoparasites specific to human hosts. They transmit epidemic typhus, trench fever and relapsing fever, diseases which have already caused millions of deaths worldwide. In order to further investigate lice vectorial capacities, laboratory-controlled live lice colonies are essential. Previously developed lice-rearing methods significantly advanced research on louse-borne diseases and louse biology. In this study, we aimed to develop a rearing technique for the Orlando (Or) strain of body lice on an artificial membrane. We tested two systems, namely the Hemotek feeding system and a Petri dish with the lice being fed through a Parafilm membrane. Lice longevity and development were drastically affected by the blood anticoagulant. Additionally, heparinised human blood on a Petri dish was the best candidate when compared to the control group (reared on a rabbit). Therefore, this strategy was applied to 500 lice. Development into adulthood was recorded after 21 days (17 days for the rabbits), and 52 eggs were deposited (240 for the rabbits). In this study, we were able to maintain one generation of body lice on an artificial membrane with comparable feeding and longevity rates to those fed on live rabbits. However, lice fecundity decreased on the artificial membrane. In vitro lice-rearing experiments will enable pathogen infection assays and pesticide bioassays to be carried out in accordance with animal welfare requirements.
Project description:Control of infestation by cosmopolitan lice (Pediculus humanus) is increasingly difficult due to the transmission of parasites resistant to pediculicides. However, since the targets for pediculicides have no been identified in human lice so far, their mechanisms of action remain largely unknown. The macrocyclic lactone ivermectin is active against a broad range of insects including human lice. Isoxazolines are a new chemical class exhibiting a strong insecticidal potential. They preferentially act on the γ-aminobutyric acid (GABA) receptor made of the resistant to dieldrin (RDL) subunit and, to a lesser extent on glutamate-gated chloride channels (GluCls) in some species. Here, we addressed the pediculicidal potential of isoxazolines and deciphered the molecular targets of ivermectin and the ectoparasiticide lotilaner in the human body louse species Pediculus humanus humanus. Using toxicity bioassays, we showed that fipronil, ivermectin and lotilaner are efficient pediculicides on adult lice. The RDL (Phh-RDL) and GluCl (Phh-GluCl) subunits were cloned and characterized by two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes. Phh-RDL and Phh-GluCl formed functional homomeric receptors respectively gated by GABA and L-glutamate with EC50 values of 16.0 μM and 9.3 μM. Importantly, ivermectin displayed a super agonist action on Phh-GluCl, whereas Phh-RDL receptors were weakly affected. Reversally, lotilaner strongly inhibited the GABA-evoked currents in Phh-RDL with an IC50 value of 40.7 nM, whereas it had no effect on Phh-GluCl. We report here for the first time the insecticidal activity of isoxazolines on human ectoparasites and reveal the mode of action of ivermectin and lotilaner on GluCl and RDL channels from human lice. These results emphasize an expected extension of the use of the isoxazoline drug class as new pediculicidal agents to tackle resistant-louse infestations in humans.
Project description:Insect reproduction is extremely variable, but the implications of alternative genetic systems are often overlooked in studies on the evolution of insecticide resistance. Both ecotypes of Pediculus humanus (Phthiraptera: Pediculidae), the human head and body lice, are human ectoparasites, the control of which is challenged by the recent spread of resistance alleles. The present study conclusively establishes for the first time that both head and body lice reproduce through paternal genome elimination (PGE), an unusual genetic system in which males transmit only their maternally derived chromosomes. Here, we investigate inheritance patterns of parental genomes using a genotyping approach across families of both ecotypes and show that heterozygous males exclusively or preferentially pass on one allele only, whereas females transmit both in a Mendelian fashion. We do however observe occasional transmission of paternal chromosomes through males, representing the first known case of PGE in which whole-genome meiotic drive is incomplete. Finally, we discuss the potential implications of this finding for the evolution of resistance and invite the development of new theoretical models of how this knowledge might contribute to increasing the success of pediculicide-based management schemes.