Dataset Information

Molecular Characteristics and Serodiagnostic Potential of Dihydrofolate Reductase from Echinococcus granulosus.

ABSTRACT: The larval stage of Echinococcus granulosus causes cystic echinococcosis (CE), a neglected tropical disease that leads to morbidity and mortality in humans and livestock worldwide. Here, we identified and characterized dihydrofolate reductase (Eg-DHFR) from E. granulosus, and evaluated its potential as a diagnostic antigen for sheep CE. Comparison between mammalian (host) DHFR and Eg-DHFR indicates that 45.7% of the 35 active site residues are different. Immunolocalisation analysis showed that native Eg-DHFR was widely distributed in all life-cycle stages of E. granulosus. Recombinant Eg-DHFR (rEg-DHFR) showed typical DHFR enzymatic parameters towards substrate, and was very sensitive to inhibition by methotrexate (IC50?=?27.75?±?1.03?nM) and aminopterin (IC50?=?63.67?±?6.76?nM). However, inhibition of DHFR exhibited little protoscolicidal effect in vitro. As there is no reliable method to monitor sheep CE, the immunogenicity of rEg-DHFR was detected, and we developed an indirect ELISA (iELISA) for CE serodiagnosis. The iELISA exhibited diagnostic specificity of 89.58%, diagnostic sensitivity of 95.83%, and the diagnostic accuracy was 91.67% compared with necropsy. Cross-reactivity assay showed analytical specificity of 85.7%. These suggest that rEg-DHFR is an effective antigen for the diagnosis of sheep CE.

SUBMITTER: Song X

PROVIDER: S-EPMC5428777 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Molecular Characteristics and Serodiagnostic Potential of Dihydrofolate Reductase from Echinococcus granulosus.

Song Xingju X Hu Dandan D Yan Min M Wang Yu Y Wang Ning N Gu Xiaobin X Yang Guangyou G

Scientific reports 20170331 1

The larval stage of Echinococcus granulosus causes cystic echinococcosis (CE), a neglected tropical disease that leads to morbidity and mortality in humans and livestock worldwide. Here, we identified and characterized dihydrofolate reductase (Eg-DHFR) from E. granulosus, and evaluated its potential as a diagnostic antigen for sheep CE. Comparison between mammalian (host) DHFR and Eg-DHFR indicates that 45.7% of the 35 active site residues are different. Immunolocalisation analysis showed that n ...[more]

PMID: 28364125

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Project description:BackgroundEchinococcoses, caused by metacestodes of Echinococcus granulosus (cystic echinococcosis; CE) and E. multilocularis (alveolar echinococcosis; AE), represent major emerging parasitic diseases. These enzootic helminthiases invoke significant public health concerns and social burdens in endemic areas. The diseases are prevalent in the Qinghai-Tibetan Plateau, China, while community-based epidemiological studies have been scarcely reported. We surveyed echinococcosis patients in the southeastern Qinghai Province, China, to better understand the concurrent epidemiological situation in this area.MethodsDuring July and August of 2013 and 2014, we screened echinococcosis patients at Yushu and Golog Prefectures, Qinghai Province, China, in a diagnostic campaign. A total of 2856 people (male:female ratio, 1:1.12; mean age, 34.6 years; age range, 6-88 years) were ultrasonographically examined for the presence of hepatic echinococcal cysts. We also collected serum samples from patients and analyzed antibody reactivity against recombinant forms of diverse E. granulosus antigen Bs (rEgAgB1-5) by enzyme-linked immunosorbent assay.ResultsWe detected 134 patients whose imaging scans were compatible with CE (115 cases) and AE (20 patients). One patient might have been infected with both CE and AE. The overall incidence was 4.7% (CE, 4.0%; AE, 0.7%). A large proportion (67.5%) of CE patients was diagnosed at active and transitional CE1-CE3 stages in their late 30s. The AE cases were generally detected at advanced stage in patients at early 20s (60%). Analysis of the receiver operating characteristic curve and Youden's index indicated that rEgAgB2 was the most promising biomarker, followed by rEgAgB3 and rEgAgB1. Overall, sensitivity and specificity of rEgAgB1-3 were 84.5-92.7% and 91.9-94.6%, respectively. rEgAgB4 and 5 showed low sensitivity with high cross-reactivity.ConclusionsOur results strongly suggest that disability-adjusted life years related to echinococcoses in Qinghai-Tibetan areas might be more serious than previously considered. Control and prevention strategy against CE and AE are highly required in these areas. In addition to ultrasonography, serological tests might provide supportive data. However, serological data should be carefully interpreted for differential diagnosis, especially in areas where both CE and AE are co-endemic.

Dataset Information

Molecular Characteristics and Serodiagnostic Potential of Dihydrofolate Reductase from Echinococcus granulosus.

Publications

Molecular Characteristics and Serodiagnostic Potential of Dihydrofolate Reductase from Echinococcus granulosus.

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