Schistosomiasis is a neglected tropical disease and the second most common parasitic disease after malaria. While praziquantel remains the primary treatment, concerns about drug resistance highlight the urgent need for new drugs and effective vaccines to achieve sustainable control. Previous proteomic studies from our group revealed that the expression of glycosyltransferase and nicastrin as proteins was higher in single-sex males than mated males, suggesting their critical roles in parasite reproduction and their potential as vaccine candidates. In this study, bioinformatic tools were employed to analyze the structural and functional properties of these proteins, including their signal peptide regions, transmembrane domains, tertiary structures, and protein interaction networks. Recombinant forms of glycosyltransferase and nicastrin were expressed and purified, followed by immunization experiments in BALB/c mice. Immunized mice exhibited significantly elevated specific IgG antibody levels after three immunizations compared to adjuvant and PBS controls. Furthermore, immunization with recombinant glycosyltransferase and nicastrin significantly reduced the reproductive capacity of female worms and liver egg burden, though egg hatchability and adult worm survival were unaffected. These findings demonstrate that recombinant glycosyltransferase and nicastrin are immunogenic and reduce female worm fecundity, supporting their potential as vaccine candidates against schistosomiasis.
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http://dx.doi.org/10.3390/pathogens14010070 | DOI Listing |
Pathogens
January 2025
National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Schistosomiasis is a neglected tropical disease and the second most common parasitic disease after malaria. While praziquantel remains the primary treatment, concerns about drug resistance highlight the urgent need for new drugs and effective vaccines to achieve sustainable control. Previous proteomic studies from our group revealed that the expression of glycosyltransferase and nicastrin as proteins was higher in single-sex males than mated males, suggesting their critical roles in parasite reproduction and their potential as vaccine candidates.
View Article and Find Full Text PDFInt J Parasitol
December 2022
National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China; Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China. Electronic address:
Schistosomiasis, which is caused by parasitic schistosomes, remains the second most prevalent parasitic disease of mammals worldwide. To successfully maintain fecundity, schistosomes have evolved a lifecycle that involves the cooperation of morphologically distinct male and female forms. Eggs produced by worm pairs are vital to the lifecycle of the parasite and are responsible for pathogenesis.
View Article and Find Full Text PDFJ Biol Chem
May 2019
From the Glycoscience and Glycotechnology Research Group, Biotechnology Research Institute for Drug Discovery, Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8568, Japan and
The type-I LacdiNAc (LDN; GalNAcβ1-3GlcNAc) has rarely been observed in mammalian cells except in the -glycan of α-dystroglycan, in contrast to type-II LDN structures (GalNAcβ1-4GlcNAc) in - and -glycans that are present in many mammalian glycoproteins, such as pituitary and hypothalamic hormones. Although a β1,3--acetylgalactosaminyltransferase 2 (B3GALNT2; type-I LDN synthase) has been cloned, the function of type-I LDN in mammalian cells is still unclear, as its carrier protein(s) has not been identified. In this study, using HeLa cells, we demonstrate that inhibition of Golgi-resident glycosyltransferase increases the abundance of B3GALNT2-synthesized type-I LDN structures, recognized by agglutinin (WFA).
View Article and Find Full Text PDFHum Mol Genet
April 2019
Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Diseases, Harvard Medical School, Charlestown, USA.
Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory skin disorder characterized clinically with acne-like lesions in apocrine gland-bearing skin, follicular occlusion and recurrent inflammation. Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. We have carried out a system review and have performed a functional analysis of the 34 unique reported HS-linked mutations in NCSTN, PSEN1, PSENEN and POGLUT1.
View Article and Find Full Text PDFBiochem Biophys Res Commun
July 2018
Laboratory of Neuropathology, Graduate School of Life and Medical Sciences, Doshisha University, Kyoto, Japan. Electronic address:
γ-Secretase complex, the assembly of nicastrin (NCT), Presenilin (PS), Presenilin Enhancer-2 (PEN-2) and Anterior pharynx defective 1 (Aph-1), catalyzes the cleavage of amyloid precursor protein to generate amyloid-β protein (Aβ), the main culprit of Alzheimer's disease. NCT becomes matured through complex glycosylation and play important role in γ-secretase activity by interacting with catalytic subunit PS. However, the role of NCT glycosylation on γ-secretase activity and substrate specificity is still unknown.
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