Dataset Information

Functionally Expression of Metalloproteinase in Taenia solium Metacestode and Its Evaluation for Serodiagnosis of Cysticercosis.

ABSTRACT:

Background

Parasite proteases have important roles in cleavage of host proteins during the invasion of host tissues and participate in the parasite's evasion from the host's immune response. The aim of the present study was to estimate a metalloproteinase properties of Taenia solium metacestode (TsMP) during host-parasite interactions, and evaluate its potential as a serodiagnostic antigen for cysticercosis.

Methods

The cDNA coding for the mature catalytic domain of TsMP was cloned into pGEX-6P-1 expression vector. A recombinant glutathione S-transferase and TsMP fusion protein was induced. After refolding and purification, enzymatic properties of the recombinant metalloproteinase were observed. Immunoblot assay was processed to evaluate its potential as a serodiagnostic antigen for cysticercosis.

Results

The recombinant TsMP protein showed proteolytic activity, which preferred host extracellular matrix proteins such as collagen and fibronectin as degradable substrates. In immunoblot assay, 87.5% of sera from patients with cysticercosis showed strong reactivity. In sera from patients with other parasitic infections and from normal controls, it showed high specificity.

Conclusions

TsMP might be involved in the processing of numerous host proteins and play an important role in the parasite life cycle. A single recombinant TsMP antigen could have a potential value for serodiagnosis of cysticercosis.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4835468 | biostudies-literature | 2016 Jan-Mar

REPOSITORIES: biostudies-literature

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Publications

Functionally Expression of Metalloproteinase in Taenia solium Metacestode and Its Evaluation for Serodiagnosis of Cysticercosis.

Zhang Ying Y Bae Young-An YA Zong Hong-Ying HY Kong Yoon Y Cai Guo-Bin GB

Iranian journal of parasitology 20160101 1

<h4>Background</h4>Parasite proteases have important roles in cleavage of host proteins during the invasion of host tissues and participate in the parasite's evasion from the host's immune response. The aim of the present study was to estimate a metalloproteinase properties of Taenia solium metacestode (TsMP) during host-parasite interactions, and evaluate its potential as a serodiagnostic antigen for cysticercosis.<h4>Methods</h4>The cDNA coding for the mature catalytic domain of TsMP was clone ...[more]

PMID: 27095967

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Project description:BackgroundTaenia solium cysticercosis is an important zoonosis in many developing countries. Human neurocysticercosis is recognised as an important cause of epilepsy in regions where the parasite occurs. However, it is largely underreported and there is a lack of data about the disease burden. Because a body of information on human and porcine cysticercosis in Cameroon is becoming available, the present study was undertaken to calculate the impact of this neglected zoonosis.MethodsBoth the cost and Disability Adjusted Life Year (DALY) estimations were applied. All necessary parameters were collected and imported in R software. Different distributions were used according to the type of information available for each of the parameters.FindingsBased on a prevalence of epilepsy of 3.6%, the number of people with neurocysticercosis-associated epilepsy was estimated at 50,326 (95% CR 37,299-65,924), representing 1.0% of the local population, whereas the number of pigs diagnosed with cysticercosis was estimated at 15,961 (95% CR 12,320-20,044), which corresponds to 5.6% of the local pig population. The total annual costs due to T. solium cysticercosis in West Cameroon were estimated at 10,255,202 Euro (95% CR 6,889,048-14,754,044), of which 4.7% were due to losses in pig husbandry and 95.3% to direct and indirect losses caused by human cysticercosis. The monetary burden per case of cysticercosis amounts to 194 Euro (95% CR 147-253). The average number of DALYs lost was 9.0 per thousand persons per year (95% CR 2.8-20.4).InterpretationThis study provides an estimation of the costs due to T. solium cysticercosis using country-specific parameters and including the human as well as the animal burden of the zoonotic disease. A comparison with a study in South Africa indicates that the cost of inactivity, influenced by salaries, plays a predominant role in the monetary burden of T. solium cysticercosis. Therefore, knowing the salary levels and the prevalence of the disease might allow a rapid indication of the total cost of T. solium cysticercosis in a country. Ascertaining this finding with additional studies in cysticercosis-endemic countries could eventually allow the estimation of the global disease burden of cysticercosis. The estimated number of DALYs lost due to the disease was higher than estimates already available for some other neglected tropical diseases. The total estimated cost and number of DALYs lost probably underestimate the real values because the estimations have been based on epilepsy as the only symptom of cysticercosis.

Project description:BackgroundNeurocysticercosis (NC) caused by Taenia solium metacestode (TsM) is a serious neurological disease of global concern. Diverse bioactive molecules involved in the long-term survival of TsM might contribute to disease progression. Fasciclin (Fas) is an extracellular protein that mediates adhesion, migration and differentiation of cells by interacting with other molecules. We hypothesized that TsMFas might bind to calcareous corpuscle (CC) through its adhesive property and participate in crucial protein-protein interactions, thus contributing to the creation of a symbiotic interactome network.MethodsTwo paralogous TsMFas (TsMFas1 and TsMFas2) were isolated, and their molecular properties were characterized. The co-localization pattern of TsMFas1 and TsMFas2 with CC was determined. CC-TsMFas binary complex was generated by incubating CC with recombinant proteins (rTsMFas1 and 2). In vitro binding assay of CC-rTsMFas1 or CC-rTsMFas2 binary complex with TsM cellular proteins extracted from scolex and neck was conducted. Their binding partners were identified through proteomic analysis. Integrated protein-protein interaction networks were established.ResultsTsMFas1 (6072 bp long) was composed of 15 exons (841 amino acid polypeptide) interrupted by 14 introns. TsMFas2 (5201 bp long) comprised of 11 exons (597 amino acids) and 10 intervening introns. These proteins displayed 22% amino acid sequence identity to each other, but tightly conserved Fas-related domains. Several isoforms of Fas1 and Fas2 proteins might have been expressed through post-translational modifications. They showed adhesion activity with other cells. TsMFas proteins were largely distributed in parenchymal regions of the scolex and bladder wall. These molecules were co-localized with CC, a unique organelle found in platyhelminths. Subsequent proteome analysis of CC-Fas binary complex mediated protein-protein interactions revealed seven protein ligands in the TsM cellular proteins. Their functions were mainly segregated into carbohydrate metabolism (enolase, phosphoenolpyruvate carboxykinase, phosphoglycerate kinase and glyceraldehyde 3-phosphate dehydrogenase) and cytoskeleton/cellular motility (actin, paramyosin and innexin nuc-9). Those proteins had direct (physical) and/or indirect (functional) relationships along with their biochemical properties and biological roles.ConclusionProtein repertoires strongly suggest that TsMFas and CC may symbiotically mediate protein-protein interactions during biological processes to maintain efficacious homeostatic functions and ensure the prolonged survival of TsM in the host.

Project description:BackgroundTaenia solium cysticercosis/taeniasis (TSCT) is reported to be endemic in pig producing areas around the world, causing significant disease burden and economic losses.MethodsThis cross-sectional study aimed at assessing Knowledge, Attitudes and Practices (KAP) regarding TSCT in four districts, namely Mbulu, Mpwapwa, Mbinga, and Rungwe in Tanzania. Data on KAP were collected through questionnaire-based interviews and household infrastructure observations.ResultsKnowledge about porcine cysticercosis was good, particularly among pig keepers across the districts. Many participants had heard about the pork tapeworm (T. solium taeniasis), and the knowledge about signs/symptoms and treatment was fair, but the means of transmission and prevention measures were often unknown. Whilst most participants were familiar with epilepsy, no one knew anything about human cysticercosis and the link between cysticercosis and epileptic seizures. A similar trend is reflected through the attitudes toward the low risk perception of cysticercosis infection. Not surprisingly, the risk perception of the infection with the pork tapeworm was low too. Many participants reported not washing their hands before eating or after using the toilet which highlights potential risks for the development of human cysticercosis. Albeit nearly every participant reported using the toilet always, household observations revealed that toilets were either lacking or had no complete walls. Generally, household observations revealed a discrepancy between questionnaire answers on the one hand and the availability of toilet and handwashing facilities and the confinement of pigs on the other hand.ConclusionThis study demonstrates knowledge gaps and adverse practices which may hinder and/or slow down the control/elimination of T. solium in endemic countries. The study results are also useful for appropriate designing of TSCT health interventions that need to be planned carefully, taking into account the local context and designing TSCT in partnership with the local communities from the beginning to the end applying a One Health approach to allow the possible sustained and best impacts.

Project description:BackgroundFatty acid (FA) binding proteins (FABPs) of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs) of Taenia solium metacestode (TsM), a causative agent of neurocysticercosis (NC), shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive.Methodology/principal findingsWe isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2), which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15-95% with other related-members. Homology modeling demonstrated a characteristic ?-barrel composed of 10 anti-parallel ?-strands and two ?-helices. TsMFABP2 harbored two additional loops between ?-strands two and three, and ?-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1) and 8.4 (TsMFABP2). Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]amino)undecannoic acid, dansyl-DL-?-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions of lipids and retinol.Conclusions/significanceThe divergent biochemical properties, physiological roles and cellular distributions of the TsMFABPs might be one of the critical mechanisms compensating for inadequate de novo FA synthesis. These proteins might exert harmonized or independent roles on lipid assimilation and intracellular signaling. The specialized distribution of retinol in the canal region further implies that cells in this region might differentiate into diverse cell types during metamorphosis into an adult worm. Identification of bioactive systems pertinent to parasitic homeostasis may provide a valuable target for function-related drug design.

Dataset Information

Functionally Expression of Metalloproteinase in Taenia solium Metacestode and Its Evaluation for Serodiagnosis of Cysticercosis.

Background

Methods

Results

Conclusions

Publications

Functionally Expression of Metalloproteinase in Taenia solium Metacestode and Its Evaluation for Serodiagnosis of Cysticercosis.

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