TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis

doi:10.1016/j.molbiopara.2011.08.003

Molecular and Biochemical Parasitology

Volume 180, Issue 2, December 2011, Pages 115-119

https://doi.org/10.1016/j.molbiopara.2011.08.003 Get rights and content

Abstract

Neurocysticercosis is an endemic parasitic disease caused by Taenia solium larva. Although the mechanism of infection is not completely understood, it is likely driven by proteolytic activity that degrades the intestinal wall to facilitate oncosphere penetration and further infection.

We analyzed the publicly available T. solium EST/DNA library and identified two contigs comprising a full-length cDNA fragment very similar to Echinococcus granulosus Ag5 protein. The T. solium cDNA sequence included a proteolytic trypsin-like-domain in the C-terminal region, and a thrombospondin type-1 adherence-domain in the N-terminal region. Both the trypsin-like and adherence domains were expressed independently as recombinant proteins in bacterial systems. TsAg5 showed marginal trypsin-like activity and high sequence similarity to Ag5. The purified antigens were tested in a Western immunoblot assay to diagnose human neurocysticercosis. The sensitivity of the trypsin-like-domain was 96.36% in patients infected with extraparenchymal cysts, 75.44% in patients infected with multiple cysts, and 39.62% in patients with a single cyst. Specificity was 76.70%. The thrombospondin type-1 adherence-domain was not specific for neurocysticercosis.

Graphical abstract

A Taenia solium recombinant antigen homologous to Echinococcus granulosus Ag5 with a trypsin-like domain and an adherence-domain is characterized and tested as an immunodiagnostics antigen.

Highlights

► TsAg5 was found in the excretory/secretory antigens of the cysticercus and in the oncosphere. ► The trypsin-like domain of TsAg5 showed a marginal proteolytic activity. ► The trypsin-like domain showed to be an important antigen for immunodiagnostics of multiple cyst and extra-parenchymal NCC. ► The adherence domain of TsAg5 was not specific.

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Financial support

This work was partially funded by research grants numbers CRP/PER08-02 from the ICGEB, P01 AI51976 TMRC, D43 TW001140 (Fogarty Training), and D43 TW007120 from the National Institutes of Health, USA. The sponsors had no role in the design or writing of this manuscript.

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The SmSP2 orthologs from S. japonicum and S. haematobium (in the genome databases annotated as mastins) were identified as antigens targeted by IgG1 in praziquantel-treated humans with acquired full resistance (Pearson et al., 2015). Remarkably, SmSP2 orthologs present in the larval stage (cysticercus) of the cestodes (Lorenzo et al., 2003; Rueda et al., 2011) were identified as major components of cyst fluid, termed Antigen 5 excretory proteins (Ag5). These Ag5 proteins are now used as a serodiagnostic test against cysticercosis (Li et al., 2012; Rueda et al., 2011).
Trematodes, also known as flukes, are phylogenetically ancient parasitic organisms. Due to their importance as human and veterinary parasites, their proteins have been investigated extensively as drug and vaccine targets. Among those, proteases, as crucial enzymes for parasite survival, are considered candidate molecules for anti-parasitic interventions. Surprisingly however, trematode serine proteases, in comparison with other groups of proteases, are largely neglected. Genes encoding serine proteases have been identified in trematode genomes in significant abundance, but the biological roles and biochemical functions of these proteases are poorly understood. However, increasing volumes of genomic and proteomic studies, and accumulated experimental evidence, indicate that this class of proteases plays a substantial role in host–parasite interactions and parasite survival. Here, we discuss in detail serine proteases at genomic and protein levels, and their known or hypothetical functions.
Cysticercosis/taeniasis endemicity in Southeast Asia: Current status and control measures
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Citation Excerpt :
In pig keeping practices, even in rural areas, it is recognized that vaccinations of farm animals can prevent pathogenic infections and therefore improve the commercial value of the pork. Recently, a vaccine for preventing porcine cysticercosis (TSOL18) has been proven to be highly effective against naturally acquired infection with T. solium in pigs in several field trials (Assana et al., 2010; Garcia et al., 2007; Gauci et al., 2012; Gonzalez et al., 2011, 2012; Jayashi et al., 2012a,b; Martinez-Ocana et al., 2011; Pina et al., 2011; Rueda et al., 2011; Verle et al., 2003; Zimic et al., 2011). It will be a great tool for combating cysticercosis (Lightowlers, 2013; WHO, 2011a).
The parasitic zoonoses cysticercosis/taeniasis is among the 17 major Neglected Tropical Diseases (NTDs) identified by the WHO as a focus for research and control. It is caused by a larval stage (cysticercus) infection of Taenia solium tapeworm in both humans and pigs. Cysticercosis occurs in many resource-poor countries, especially those with warm and mild climates in the regions of Latin America (LA), Asia and Sub-Saharan Africa (SSA). The prevalence of human cysticercosis is marked in those areas where individuals are traditionally keen to consume raw or insufficiently cooked pork and/or where the husbandry of pigs is improper. The worldwide burden of cysticercosis is unclear and notably, large-scale control initiatives are lacking in all regions. This review focuses on the current endemic status of cysticercosis caused by T. solium infection in both humans and pigs living in 13 Southeast Asian countries. We will also emphasize epidemiological data as well as prevention and control of human neurocysticercosis.
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¹: For the Cysticercosis Working Group in Peru.

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Molecular and Biochemical Parasitology

Abstract

Graphical abstract

Highlights

Section snippets

Financial support

References (23)

Cysticercosis as a major cause of epilepsy in Peru. The Cysticercosis Working Group in Peru (CWG)

Lancet

Parasite proteases

Exp Parasitol

Subunit composition and specificity of the major cyst fluid antigens of Echinococcus granulosus

Mol Biochem Parasitol

ORF-FINDER: a vector for high-throughput gene identification

Gene

A combined transmembrane topology and signal peptide prediction method

J Mol Biol

Immunodiagnosis of Taenia solium taeniosis/cysticercosis

Trends Parasitol

Hymenolepis nana infection: symptoms and response to nitazoxanide in field conditions

Trans R Soc Trop Med Hyg

Taenia saginata oncosphere excretory/secretory peptidases

J Parasitol

Comparison of the peptidase activity in the oncosphere excretory/secretory products of Taenia solium and Taenia saginata

J Parasitol

Echinococcus granulosus antigen 5 is closely related to proteases of the trypsin family

Biochem J

Prediction of lipoprotein signal peptides in Gram-negative bacteria

Protein Sci

Cited by (10)

Serine proteases in schistosomes and other trematodes

Cysticercosis/taeniasis endemicity in Southeast Asia: Current status and control measures

Trends in the diagnosis of human neurocysticercosis: Issues and challenges

Treatment of neurocysticercosis: Current and future options

SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties

Proteases of parasitic helminths: Their metabolic role in establishment of infection in the host

Short communicationTsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis

Abstract

Graphical abstract

Highlights

Section snippets

Financial support

Lancet

Exp Parasitol

Mol Biochem Parasitol

Gene

J Mol Biol

Trends Parasitol

Trans R Soc Trop Med Hyg

Taenia saginata oncosphere excretory/secretory peptidases

J Parasitol

Comparison of the peptidase activity in the oncosphere excretory/secretory products of Taenia solium and Taenia saginata

J Parasitol

Echinococcus granulosus antigen 5 is closely related to proteases of the trypsin family

Biochem J

Prediction of lipoprotein signal peptides in Gram-negative bacteria

Protein Sci

Short communication
TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis