Pathogens, 06 January 2023 doi.org: 10.3390/pathogens12010095

Samuel C. Uzoechi¹, Bruce A. Rosa¹, Kumar Sachin Singh¹, Young-Jun Choi¹, Bethany K. Bracken², Paul J. Brindley³ , R. Reid Townsend⁴, Robert Sprung⁴, Bin Zhan⁵, Maria-Elena Bottazzi⁵, John M. Hawdon³, Yide Wong⁶, Alex Loukas⁶, Sergej Djuranovic⁷ and Makedonka Mitreva^1*

Intricate molecular communication between schistosome flatworms and their mammalian host, as well as between paired male and female schistosomes has shaped the secreted proteome of these flatworms. Whereas the schistosome egg is responsible for the disease manifestations of chronic schistosomiasis, the long lived, adult female and male stages also release different mediators including glycans, lipids, proteins and small molecules, known as excretory/secretory products (ESPs), that facilitate their survival. Given their importance, deeper analysis focused on analyzing the ESPs from adult schistosomes would likely be informative, beyond current understanding of the complement of ESP proteins. Here, taking advantage of highly accurate and sensitive mass spectrometers, the excretory/secretory proteome from cultured Schistosoma mansoni male or female adult worms was identified, quantified, compared and contrasted using a label-free proteomic approach. Approximately 1,000 proteins were identified, from which almost 800 could be quantified. Considering the proteins uniquely identified and proteins with a significantly regulated expression pattern in male or female flukes, a total of 370 and 140 proteins were uniquely or more abundantly secreted by males and females, respectively. Using functional analysis networks showing the gene ontology terms and KEGG pathways with the highest significance, we observed that male schistosomes secrete proteins related to carbohydrate metabolism and cytoskeletal organization more abundantly than females, while female worms secreted more hydrolases and proteins involved in cellular homeostasis than males. This analysis doubles the number of reported excreted/secreted proteins from S. mansoni, contributing to deeper understanding of the host-parasite interaction and parasitism. Furthermore, these findings expand potential vaccine and diagnostic candidates for this neglected tropical disease pathogen, and thereby also provide leads for novel intervention to control this disease and its transmission.

¹ Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
² Charles River Analytics, Inc., Cambridge, MA 02138, USA
³ Department of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA
⁴ Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
⁵ Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA
⁶ Centre for Molecular Therapeutics, Australian Institute of Tropical Health andMedicine, James Cook University, Cairns 4878, Australia
⁷ Department of Cell Biology and Physiology, Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
^* Correspondence: mmitreva@wustl.edu

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