This could, at least in part, explain the PZQ sensitivity of adult cestodes. Although PZQ resistance will most probably never be an issue in the treatment of taeniasis patients, it could become a problem in large scale deworming campaigns against E. multilocularis, E. granulosus and Mesocestoides spp. that have been suggested already for parts Vemurafenib order of Central Europe and China (25,65,66). Particularly for such projects, genetic information on the cellular targets of PZQ, as available through the genome projects, will be highly valuable in assessing treatment efficacy and the emergence of drug resistance. In sharp contrast to its activity on adult cestodes, PZQ has very limited effects

on metacestode stages (67). The underlying

reason could be that the calcium channel β subunits selleck chemical (or other potential PZQ targets) are expressed in an adult-specific manner, and in the currently available transcriptome profiles for E. multilocularis metacestode vesicles, the respective genes are indeed expressed at a marginal level (data not shown). Because of the low efficacy of PZQ treatment, the current drugs of choice in chemotherapy against AE, CE and NCC are BZs that have a high affinity for helminth-specific β-tubulin isoforms, thus inhibiting microtubule polymerization that eventually leads to parasite death. Although prolonged BZ treatment of the intermediate host can be effective in eliminating E. granulosus cysts or T. solium cysticerci (68,69), its activity against E. multilocularis is very limited. In AE, BZ treatment is mostly parasitostatic rather than parasitocidal and, as a consequence, has to be given lifelong Florfenicol (68). Furthermore, in all three types of infection, BZ treatment can be associated with severe side effects that are due

to limited bioavailability of the drug at the site of infection and high structural homology of β-tubulin of parasite and host. Three major β-tubulin isoforms that are expressed by E. multilocularis have already been characterized several years ago and were shown to be highly homologous (>90% amino acid identity) to β-tubulin of humans (40; Table 2). In the E. multilocularis genome assembly, we have identified at least nine β-tubulin encoding loci, although transcriptome profiling clearly shows that the three previously identified isoforms (40) are abundantly expressed in all larval stages, whereas the other six loci are mostly silent or may even represent pseudogenes. Studies on mechanisms of BZ resistance and sensitivity in nematodes previously identified two amino acid residues (Phe200 and Phe167 in BZ-sensitive isoforms) that are particularly important for drug binding to β-tubulin. In BZ-resistant strains of Haemonchus contortus, these residues were frequently exchanged by Tyr or His, leading to diminished BZ binding (70).