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

Abstract

BackgroundHuman 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.MethodsWe 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.ResultsMultiple 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.ConclusionGiven 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.

Evaluative Profiling of Arsenic Sensing and Regulatory Systems in the Human Microbiome Project Genomes

“…Proteins for water and/or glycerol transport across cellular membranes termed aquaporins can also function in arsenic transport 21. The USP family is a protein family known to enable bacteria, archaea, fungi, viridiplantae, and certain metazoans that respond to stresses 22–24. The USP family includes proteins that contain 140–160 amino acid (aa) USP domain [PF00582 (or Pfam00582) in the Pfam database] 22–24.…”

“…The USP family is a protein family known to enable bacteria, archaea, fungi, viridiplantae, and certain metazoans that respond to stresses 22–24. The USP family includes proteins that contain 140–160 amino acid (aa) USP domain [PF00582 (or Pfam00582) in the Pfam database] 22–24. The domain architecture of USPs can be (i) one USP domain, (ii) two USP domains in tandem, or (iii) one or two USP domains together with other functional domains including transporters, kinases, permeases, transferases, and bacterial sensor 24,25.…”

Identification of Functional Regulatory Residues of theβ-Lactam Inducible Penicillin Binding Protein in Methicillin-ResistantStaphylococcus aureus

“…The Glu residue has been document as one of the essential residue sites involved when metals bind to proteins [76, 77], and Ser is also known as one of the key phosphorylation residues in proteins [78–80]. Metallic ions have been demonstrated as essential contributors to protein phorphorylation [81–85]. This suggests that in PBP-2′ gene transpeptidase activity might involved or could be regulated by phorphorylation through the binding of metallic ions as ligands.…”

An immunoinformatics approach for the design of a multi-epitope subunit vaccine for urogenital schistosomiasis

“…Masamba et al (2016) has proposed that selective identification of small molecule inhibitors or peptides as an inhibitor of HSPs at the schistosomula stage could be useful in targeting and preventing re-infection of schistosomiasis. Parasites use several mechanisms to upregulate Universal Stress Proteins (including HSPs) which assist the parasite to tolerate different environmental and adverse conditions especially at the schistosomula stage of parasite development (Mbah et al, 2013). The HSPs CTL and HTL epitopes with predicted high immunogenicity were selected for inclusion in the vaccine construct.…”

“…By transiting between intra-mammalian, aquatic and snail stages to develop into full maturity, schistosomes face a number of hostile environments throughout their lifecycle (Mbah et al, 2013) and heat shock responses have been associated with cellular stress during the movement of parasite from a cooler, low saline and freshwater environment to a warmer, saline environment of a human host (Devaney, 2006;Mbah et al, 2013).…”