Echinococcus multilocularis and Other Taeniid Metacestodes of Muskrats in Luxembourg: Prevalence, Risk Factors, Parasite Reproduction, and Genetic Diversity.

Muskrats (Ondatra zibethicus) are competent intermediate hosts for Echinococcus multilocularis, are frequently infected with this zoonotic cestode, and have even been proposed as a target species to monitor endemicity levels of this parasite. However, their contribution to maintaining the parasitic lifecycle is still unclear. To obtain data on infection frequency and reproductive potential, 280 muskrats from the Grand Duchy of Luxembourg were examined for cestode larvae in the years 2013−2017. Based on morphological and molecular identification, Echinococcus multilocularis was found at a prevalence of 14.6%. Other metacestodes were Hydatigera kamiyai, with a prevalence of 45.7%, Taenia martis with 8.9%, Taenia polyacantha with 5.0%, and Versteria mustelae, which was found in 0.7% of all muskrats. More than 80% of E. multilocularis-infected muskrats contained fertile metacestodes with a mean number of >300,000 (and up to 1,609,816) protoscoleces, which is by far the highest reproductive potential known from any intermediate host species in Europe. Temporal analysis of E. multilocularis prevalence within the study period (and in comparison with earlier data) strongly indicates a robust increase in the studied area. Host age seemed to be an important risk factor for infection, as well as co-infections with Hydatigera kamiyai. A preference for the right medial lobe of the liver as the location of E. multilocularis metacestode was observed. Intraspecific genetic variation among 89 discrete E. multilocularis metacestodes was non-existent based on 300−1590 bp sections of cox1. This is a stark contrast to H. kamiyai, of which nine haplotypes were found on a short 318 bp section of cox1, resulting in genetic diversity in the small country of Luxembourg at a similar level than previously reported from large stretches of Europe and northern Asia.

Molecular insight on the altered membrane trafficking of TrkA kinase dead mutants.

We address the contribution of kinase domain structure and catalytic activity to membrane trafficking of TrkA receptor tyrosine kinase. We conduct a systematic comparison between TrkA-wt, an ATP-binding defective mutant (TrkA-K544N) and other mutants displaying separate functional impairments of phosphorylation, ubiquitination, or recruitment of intracellular partners. We find that only K544N mutation endows TrkA with restricted membrane mobility and a substantial increase of cell surface pool already in the absence of ligand stimulation. This mutation is predicted to drive a structural destabilization of the αC helix in the N-lobe by molecular dynamics simulations, and enhances interactions with elements of the actin cytoskeleton. On the other hand, a different TrkA membrane immobilization is selectively observed after NGF stimulation, requires both phosphorylation and ubiquitination to occur, and is most probably related to the signaling abilities displayed by the wt but not mutated receptors. In conclusion, our results allow to distinguish two different TrkA membrane immobilization modes and demonstrate that not all kinase-inactive mutants display identical membrane trafficking.