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In-depth proteomic characterization of Schistosoma haematobium: towards the development of new tools for elimination

View ORCID ProfileJavier Sotillo, View ORCID ProfileMark S. Pearson, Luke Becker, Gebeyaw G. Mekonnen, View ORCID ProfileAbena S. Amoah, View ORCID ProfileGovert van Dam, View ORCID ProfilePaul L.A.M. Corstjens, View ORCID ProfileTakafira Mduluza, View ORCID ProfileFrancisca Mutapi, View ORCID ProfileAlex Loukas
doi: https://doi.org/10.1101/486662
Javier Sotillo
1Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
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  • For correspondence: javier.sotillo@jcu.edu.au alex.loukas@jcu.edu.au
Mark S. Pearson
1Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
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Luke Becker
1Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
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Gebeyaw G. Mekonnen
1Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
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Abena S. Amoah
2Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
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Govert van Dam
2Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
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Paul L.A.M. Corstjens
3Department of Molecular Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
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Takafira Mduluza
4Biochemistry Department, University of Zimbabwe, Mount Pleasant, Harare, Zimbabwe
5TIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA), University of Zimbabwe
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Francisca Mutapi
5TIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA), University of Zimbabwe
6Institute of Immunology & Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, King’s Buildings, Edinburgh, UK
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Alex Loukas
1Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
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  • For correspondence: javier.sotillo@jcu.edu.au alex.loukas@jcu.edu.au
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Abstract

Background Schistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S. haematobium infection can cause different urogential clinical complications, particularly in the bladder, and furthermore, this parasite has been strongly linked with squamous cell carcinoma. A comprehensive analysis of the molecular composition of its different proteomes will contribute to developing new tools against this devastating disease.

Methods and Findings By combining a comprehensive protein fractionation approach consisting of OFFGEL electrophoresis with high-throughput mass spectrometry, we have performed the first in-depth characterisation of the different discrete proteomes of S. haematobium that are predicted to interact with human host tissues, including the secreted and tegumental proteomes of adult flukes and secreted and soluble egg proteomes. A total of 662, 239, 210 and 138 proteins were found in the adult tegument, adult secreted, soluble egg and secreted egg proteomes, respectively. In addition, we probed these distinct proteomes with urine to assess urinary antibody responses from naturally infected human subjects with different infection intensities, and identified adult fluke secreted and tegument extracts as being the best predictors of infection.

Conclusion We provide a comprehensive dataset of proteins from the adult and egg stages of S. haematobium and highlight their utility as diagnostic markers of infection intensity for the development of novel tools to control this important neglected tropical disease.

Author Summary Schistosomiasis is a neglected tropical disease affecting millions of people worldwide. Of the main three species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. This parasite can cause a range of clinical complications associated with bladder pathogenesis, including squamous cell carcinoma as well as genital malignancy in women. Herein, we have performed the first comprehensive characterisation of the proteins implicated in host-parasite interactions (secreted and surface proteins from the adult flukes and secreted and soluble egg proteins) in order to advance our understanding of the parasite’s biology. Furthermore, we have characterised the different antibody responses in urine from infected human subjects from an endemic area presenting different infection intensities. The data obtained in this study can be used as a first step towards the development of novel tools for the control of urogenital schistosomiasis.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 10, 2018.
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In-depth proteomic characterization of Schistosoma haematobium: towards the development of new tools for elimination
Javier Sotillo, Mark S. Pearson, Luke Becker, Gebeyaw G. Mekonnen, Abena S. Amoah, Govert van Dam, Paul L.A.M. Corstjens, Takafira Mduluza, Francisca Mutapi, Alex Loukas
bioRxiv 486662; doi: https://doi.org/10.1101/486662
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In-depth proteomic characterization of Schistosoma haematobium: towards the development of new tools for elimination
Javier Sotillo, Mark S. Pearson, Luke Becker, Gebeyaw G. Mekonnen, Abena S. Amoah, Govert van Dam, Paul L.A.M. Corstjens, Takafira Mduluza, Francisca Mutapi, Alex Loukas
bioRxiv 486662; doi: https://doi.org/10.1101/486662

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