Dr.Hong You
QIMR Berghofer Medical Research Institute, Australia
Title: Functional characterisation of Schistosoma japonicum acetylcholinesterase
Biography
Biography: Dr.Hong You
Abstract
Acetylcholinesterase (AChE) is an important metabolic enzyme of schistosomes present in the musculature and on the surface of the blood stage. As both target for the antischistosomal drug metrifonate and as a potential vaccine candidate, AChE has been characterized in the schistosome species Schistosoma mansoni, S. haematobium and S. bovis but not S. japonicum. In this study, we report the full-length cDNA sequence and describe phylogenetic and molecular structural analysis to facilitate understanding of the biological function of AChE (SjAChE) in S. japonicum. The protein has high sequence identity (88%) with the AChEs in S. mansoni, S. haematobium and S. bovis and has 25% sequence similarity with human AChE, suggestive of a highly specialized role for the enzyme in both parasite and host. We immunolocalized SjAChE and demonstrated its presence on the surface of adult worms and schistosomula, as well as its lower expression in parenchymal regions. The relatively abundance of AChE activity (90%) present on the surface of adult S. japonicum when compared with that reported in other schistosomes suggests SjAChE may be a more effective drug or immunological target against this species. We also demonstrate that the classical inhibitor of AChE, BW285c51, inhibited AChE activity in tegumental extracts of paired worms, single males and single females by 59%, 22% and 50%, respectively. These results build on previous studies in other schistosome species indicating major differences in the enzyme between parasite and mammalian host and provide further support for the design of an anti-schistosome intervention targeting AChE.