Inferences on the biochemical and environmental regulation of universal stress proteins from Schistosomiasis parasites

Andreas N Mbah,^1,2 Ousman Mahmud,¹ Omotayo R Awofolu,² Raphael D Isokpehi<sup>1

1</sup>Center for Bioinformatics and Computational Biology, Department of Biology, Jackson State University, Jackson, MS, USA; ²Department of Environmental Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Pretoria, South Africa

Background: Human schistosomiasis is a freshwater snail-transmitted disease caused by parasitic flatworms of the Schistosoma genus. Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum are the three major species infecting humans. These parasites undergo a complex developmental life cycle, in which they encounter a plethora of environmental signals. The presence of genes encoding the universal stress protein (USP) domain in the genomes of Schistosoma spp. suggests these flatworms are equipped to respond to unfavorable conditions. Though data on gene expression is available for USP genes, their biochemical and environmental regulation are incompletely understood. The identification of additional regulatory molecules for Schistosoma. USPs, which may be present in the human, snail, or water environments, could also be useful for schistosomiasis interventions.
Methods: We developed a protocol that includes a visual analytics stage to facilitate integration, visualization, and decision making, from the results of sequence analyses and data collection on a set of 13 USPs from S. mansoni and S. japonicum.
Results: Multiple sequence alignment identified conserved sites that could be key residues regulating the function of USPs of the Schistosoma spp. Based on the consistency and completeness of sequence annotation, we prioritized for further research the gene for a 184-amino-acid-long USP that is present in the genomes of the three human-infecting Schistosoma spp. Calcium, zinc, and magnesium ions were predicted to interact with the protein product of the gene.
Conclusion: Given that the initial effects of praziquantel on schistosomes include the influx of calcium ions, additional investigations are required to (1) functionally characterize the interactions of calcium ions with the amino acid residues of Schistosoma USPs; and (2) determine the transcriptional response of Schistosoma. USP genes to praziquantel. The data sets produced, and the visual analytics views that were developed, can be easily reused to develop new hypotheses.

Keywords: ATP binding protein, calcium, functional sites, praziquantel, Schistosoma, schistosomiasis