Inhibition of Schistosoma mansoni ether-a-go-go related gene-encoded potassium channels leads to hypermotility and impaired egg production.

The purpose of this work was to investigate the effect of ether-a-go-go related gene (ERG) potassium channel inhibition on Schistosoma mansoni. Use of dofetilide to block the schistosome ERGs resulted in a striking 'corkscrew' effect. The worms were unable to control their motility; they were hypermotile. The treated worms produced abnormal eggs, some of which consisted of little more than a spine. One of the S. mansoni ERGs (SmERGs), Smp_161140, was chosen for further study by RNAi. The transcript was knocked down to 50% compared to the controls. These RNAi-treated worms demonstrated seizure-like movements. In S. mansoni, as in other organisms, ERG channels seem to play a role in regulating muscle excitability. This work shows that egg production can be greatly reduced by effectively targeting muscle coordination in these important parasites.

Identification, isolation and characterization of a Fyn-like tyrosine kinase from Schistosoma mansoni.

Growth and development of adult schistosomes requires permanent communication processes of the parasites with their specific host environment and, additionally, between the two genders. Accumulating evidence suggests that, at the molecular level, the mandatory interactions are mediated by signal transduction processes. During recent years, a considerable interest has emerged in the identification of signalling molecules from this parasite and to elucidate their roles during development. In this organism, a number of different molecules have been identified which belong to diverse classes of evolutionary conserved signal transduction cascades. However, up to now no representative of the conserved family of cellular tyrosine kinases has been identified. In this study we present a suitable approach to identify this class of molecules and demonstrate the successful cloning and molecular characterization of one of the isolated genes, the tyrosine kinase 5 (TK5). An unexpected finding was that in the Liberian strain of Schistosoma mansoni the TK5 gene exhibits an allelic polymorphism.