Genome-wide analysis of regulatory proteases sequences identified through bioinformatics data mining in Taenia solium

Abstract

BackgroundCysticercosis remains a major neglected tropical disease of humanity in many regions, especially in sub-Saharan Africa, Central America and elsewhere. Owing to the emerging drug resistance and the inability of current drugs to prevent re-infection, identification of novel vaccines and chemotherapeutic agents against Taenia solium and related helminth pathogens is a public health priority. The T. solium genome and the predicted proteome were reported recently, providing a wealth of information from which new interventional targets might be identified. In order to characterize and classify the entire repertoire of protease-encoding genes of T. solium, which act fundamental biological roles in all life processes, we analyzed the predicted proteins of this cestode through a combination of bioinformatics tools. Functional annotation was performed to yield insights into the signaling processes relevant to the complex developmental cycle of this tapeworm and to highlight a suite of the proteases as potential intervention targets.ResultsWithin the genome of this helminth parasite, we identified 200 open reading frames encoding proteases from five clans, which correspond to 1.68% of the 11,902 protein-encoding genes predicted to be present in its genome. These proteases include calpains, cytosolic, mitochondrial signal peptidases, ubiquitylation related proteins, and others. Many not only show significant similarity to proteases in the Conserved Domain Database but have conserved active sites and catalytic domains. KEGG Automatic Annotation Server (KAAS) analysis indicated that ~60% of these proteases share strong sequence identities with proteins of the KEGG database, which are involved in human disease, metabolic pathways, genetic information processes, cellular processes, environmental information processes and organismal systems. Also, we identified signal peptides and transmembrane helices through comparative analysis with classes of important regulatory proteases. Phylogenetic analysis using Bayes approach provided support for inferring functional divergence among regulatory cysteine and serine proteases.ConclusionNumerous putative proteases were identified for the first time in T. solium, and important regulatory proteases have been predicted. This comprehensive analysis not only complements the growing knowledge base of proteolytic enzymes, but also provides a platform from which to expand knowledge of cestode proteases and to explore their biochemistry and potential as intervention targets.Electronic supplementary materialThe online version of this article (doi: 10.1186/1471-2164-15-428) contains supplementary material, which is available to authorized users.

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part I: Helminths

“…In addition to caspases and cathepsins identified in the previous studies,Yan and his colleagues [150] identified other CPs in T. solium genome such as several members of sapiens (clan CA) including calpain, ubiquitinyl hydrolase-L1 and ubiquitin-specific peptidase 14 representing families C2, C12 and C19, respectively. The investigators discussed their findings and predicted the characters and roles played by CPs expression using phylogenetic analysis and with comparison with similar CPs detected in other helminths such as E. multilocularis, S. mansoni, and Caenorhabditis elegans as models for of different helminth' classes.…”

Genome-wide identification and structure-function studies of proteases and protease inhibitors in Cicer arietinum (chickpea)

“…Previously Yan et al reported the genome-wide analysis of regulatory proteases in Taenia solium genome [12]. However, in our study, an in silico search of both proteases and PIs together in chickpea genome was conducted.…”

Neurocysticercosis and the Central Nervous System: Advancements in Diagnosis, Treatment, and Future Prospects

“…The crystal structure of recombinant T. s o l i u m Cu/Zn-SOD was this organism's first reported protein structure. T. s o l i u m expresses cytosolic Cu, Zn superoxide dismutase, a 2-Cys peroxiredoxin, and two glutathione transferase isoforms, all proven to protect mice against cysticercosis [70]. Their presence throughout developmental and adult stages highlights the pivotal role of antioxidant enzymes in T. s o l i u m physiology, suggesting potential for novel drug development.…”

“…Yan et al [70] conducted a study identifying 197 novel proteases in T. s o l i u m , belonging to 37 families [69,70]. These proteases were classified based on the active site amino acid residue into categories like aspartic, cysteine, serine, metallo-serine, and threonine proteases.…”