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

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 urogenital 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. Protein composition was markedly different between the different extracts, highlighting the distinct subsets of proteins that different development stages present in their different niches. Furthermore, we have identified adult fluke ES and tegument extracts as best predictors of infection using urine antibodies of naturally infected people. This study provides the first steps towards the development of novel tools to control this important neglected tropical disease.

C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis inSchistosoma japonicum-Infected Mice

“…Researchers found that glycoproteins such as IPSE (SmEP-25) [42], omega-1 [43], and kappa-5 [44] secreted by S. mansoni eggs and Sm29 [45] secreted by S. haematobium stimulate Th2 cytokine production in mice. For S. japonicum , egg secretory proteins (ESP) instead of IPSE, omega-1, and kappa-5 played a central role in driving the development of the immune response to the Th2 pattern because it was predicted to stimulate the production of IL-1, IL-3, IL-5, IL-4, and IL-13 [46].…”

A Review of Nanotechnology for Targeted Anti-schistosomal Therapy

“…They may likely also be responsible for the dramatic changes in niche environments of the earlier stages of intra-mammalian schistosomula development. Braschi et al, 2006a,b;Van Hellemond et al, 2006;Sotillo et al, 2015Sotillo et al, , 2016Sotillo et al, , 2019 Enzymes (Esterases, carbonic anhydrase, Phosphodrolases, Thoredoxin peroxidase, Glyceraldehyde-3-phosphate dehydrogenase, protein disulfide isomerase, Glutathione S-transferase etc. )…”

“…All other enzymes found on schistosomes tegument contribute toward the survival of the schistosomes. Braschi et al, 2006a;Van Hellemond et al, 2006;Mulvenna et al, 2010;Sotillo et al, 2015Sotillo et al, , 2016Sotillo et al, , 2019 McKenzie et al 2017, where the uptake of glucose was regulated in Schistosoma mansoni by Akt/Protein kinase B signaling. It was observed that Akt can be triggered by the host L-arginine, more so, insulin was shown to be effective in the layer of adult and schistosomula teguments.…”

“…Similarly, the schistosome tegument possess proteins which have no sequence similarity with any other sequence found in databases of species excepts in schistosomes (Van Hellemond et al, 2006). Several other studies (Liu et al, 2006;Pérez-Sánchez et al, 2006;Mulvenna et al, 2010;Castro-Borges et al, 2011;Sotillo et al, 2016Sotillo et al, , 2019 have employed proteomics technique in identification of several molecular receptors which are druggable and vaccine candidates for schistosomiasis treatment.…”

Schistosoma haematobiumextracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

“…One of the main strategies the parasite’s employ to hijack the immune effector response is to release a suite of immunomodulatory excretory/secretory (ES) products. ES products comprise different proteins, glycans, lipids, and nucleic acids [14], and have been the focus of different studies aiming at understanding the molecular basis of host-parasite interactions and the subsequent use of this information to develop novel therapeutics and diagnostics [15-18]. Recently, it has been documented that the ES products from different helminths (including schistosomes) contain extracellular vesicles (EV)s [19-22].…”