Exploring strategies and approaches to schistosomiasis control and elimination - the role of basic and applied research

Bc. Enoch Mensah Boateng

Doctoral thesis

Abstract:

Schistosomiasis, a waterborne parasitic disease affects over 200 million of people and 700 million more people are at risk of infection. Schistosoma mansoni, Schistosoma haematobium and Schistosoma japonicum are the predominant species causing human schistosomiasis. The disease is deadly if left untreated. Currently the only chemotherapy against schistosomiasis is praziquantel which is mass administered to vulnerable population in endemic communities. The drug has been in used for estimated 40 decades and the indiscriminate use it has raised concerns of reduced efficacy or emergence of resistance species. There is no vaccine or alternative drug for treating schistosomiasis despite several shortcomings of praziquantel. In this study, S. mansoni is used as a model organism to study yet unrevealed functions of human glutamate carboxypeptidase II (GCPII). GCP2 and its related paralogs have been extensively studied in mammalian systems for their biomedical potentials. However, their full functions remain elusive due to the complexity of the mammalian systems as the have other genes coding paralogs of human GCPII. S. mansoni being a simple system with only a single gene coding GCPII ortholog, S. mansoni is hence ideal for revealing the primary function of the protein before later diversification. In this study, SmM28B is recombinantly expressed in E. coli bacterial, purified and used to produced anti-rabbit polyclonal antibody. The antibody was used for immunolocalization in adult female, male and knockdown schistosomula. The protein was found to be localized in esophageal gland, ventral sucker, testes, gastrodermis, ovary, oviduct, parenchyma cells and vitellaria. Although in vitro gene silencing was 95% successful, the gene silencing did not yield any phenotypic significant difference in vivo when mice were infected with knockdown schistosomula. The result shows that SmM28B protein is localized in functionally similar organs/tissues as their mammalian ortholog, However, further study might be necessary to reveal the exact function of SmM28B in parasitism in general and S. mansoni in specific.

Keywords

Schistosomiasis, Schistosoma mansoni, Peptidases, Parasitic diseases, Glutamate carboxypeptidase II, immunolocalization, Neglected tropical diseases

Language used: English

Date on which the thesis was submitted / produced: 2. 6. 2023

Thesis defence

• Supervisor: RNDr. Jan Dvořák, Ph.D.
• Reader: Martin Horn, externi, Roman Kuchta, externi, Libor Mikeš, externi

Czech University of Life Sciences Prague

Faculty of Agrobiology, Food and Natural Resources

Doctoral programme:
Applied Zoology