Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni In Vitro exhibiting pleiotropic effects

Abstract

Schistosomiasis is an infectious disease caused by schistosome parasites, affecting millions of people worldwide. The pathogenic consequences of schistosomiasis are caused by the eggs inducing severe organ inflammations. Praziquantel is widely used to treat schistosomiasis; however, there is fear of resistance developing. Research in the last decades has provided strong evidence for the importance of protein kinases controlling physiological processes in schistosomes. Two Abl-kinases were discovered, whose activities are blocked by Imatinib, an inhibitor known as Gleevec/Glivec from human cancer therapy. In vitro, Imatinib treatment led to dramatic effects on morphology and physiology and to the death of adult schistosomes. Besides modeling of the schistosome Abl-kinases we investigated the effect of Imatinib on gene expression in adult S. mansoni by performing transcriptomics and discovered a wide influence on the transcription of genes involved in surface-, muscle-, gut- and gonad-associated processes. Comparative in silico analyses with data from a previous study indicated a yet unknown association of TGFß and Abl-kinase signaling in schistosomes. Among others the gynecophoral canal protein gene GCP was identified as a common target. The data obtained demonstrate a substantial influence of Imatinib on physiological processes in adult schistosomes supporting the role of protein kinases as interesting targets.