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|Sun Yat-sen University, China|
|ScientificTracks Abstracts: J Bacteriol Parasitol|
|Clonorchiasis, caused by Clonorchis sinensis infection, is a kind of neglected tropical disease. Approximately 35 million people are infected with C. sinensis globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study. CsHK possesses typical characteristics of nonmammalian HKs regarding the amino acid sequence and spatial structure. rCsHK is a homotrimer and a distinct 50 kDa G6P-sensitive allosteric HK. There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP and citrate) and a small molecular inhibitor (2-phenyl-1, 2-benzisoselenazol-3(2H)-one, EbSe) regulated the enzymatic activity of rCsHK and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro. Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, shows potential as a vaccine and as a promising drug target for clonorchiasis.|
Tingjin Chen has obtained his PhD degree from Department of Parasitology at Sun Yat-sen University in 2015. He has developed a research program that provides new ideas for vaccine development against C. sinensis infection.
Email: [email protected]
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