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Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis.

ABSTRACT: Fasciola hepatica is considered an emergent human pathogen, causing liver fibrosis or cirrhosis, conditions that are known to be direct causes of cancer. Some parasites have been categorized by WHO as carcinogenic agents such as Opisthorchis viverrini, a relative of F. hepatica. Although these two parasites are from the same class (Trematoda), the role of F. hepatica in carcinogenesis is unclear. We hypothesized that F. hepatica might share some features with O. viverrini and to be responsible to induce proliferation of host cells. We analyzed the recently released genome of F. hepatica looking for a gene coding a granulin-like growth factor, a protein secreted by O. viverrini (Ov-GRN-1), which is a potent stimulator of proliferation of host cells. Using computational biology tools, we identified a granulin-like molecule in F. hepatica, here termed FhGLM, which has high sequence identity level to Ov-GRN-1 and human progranulin. We found evidence of an upstream promoter compatible with the expression of FhGLM. The FhGLM architecture showed to have five granulin domains, one of them, the domain 3, was homologue to Ov-GRN-1 and human GRNC. The structure of the FhGLM granulin domain 3 resulted to have the overall folding of its homologue the human GRNC. Our findings show the presence of a homologue of a potent modulator of cell growth in F. hepatica that might have, as other granulins, a proliferative action on host cells during fascioliasis. Future experimental assays to demonstrate the presence of FhGLM in F. hepatica are needed to confirm our hypothesis.

SUBMITTER: Machicado C

PROVIDER: S-EPMC4912509 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis.

Machicado Claudia C Marcos Luis A LA Zimic Mirko M

SpringerPlus 20160617 1

Fasciola hepatica is considered an emergent human pathogen, causing liver fibrosis or cirrhosis, conditions that are known to be direct causes of cancer. Some parasites have been categorized by WHO as carcinogenic agents such as Opisthorchis viverrini, a relative of F. hepatica. Although these two parasites are from the same class (Trematoda), the role of F. hepatica in carcinogenesis is unclear. We hypothesized that F. hepatica might share some features with O. viverrini and to be responsible t ...[more]

PMID: 27386259

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Project description:BackgroundFasciola hepatica (liver fluke) affects grazing animals including horses but the extent to which it affects UK horses is unknown.ObjectivesTo define how liver fluke affects the UK horse population.Study designDescriptive, cross-sectional, observational study.MethodsAn F. hepatica excretory-secretory antibody detection ELISA with a diagnostic sensitivity of 71% and specificity of 97% was validated and used to analyse serum samples. An abattoir study was performed to determine prevalence. A case-control study of 269 horses compared fluke exposure between horses with liver disease and controls. Data on clinical signs and blood test results were collected for sero-positive horses. Genotyping of adult fluke was used to produce a multilocus genotype for each parasite.ResultsFour (2.2%) of 183 horses registered in the UK, sampled in the abattoir, had adult flukes in the liver, and the sero-prevalence of F. hepatica was estimated as 8.7%. In the case-control study, horses showing signs consistent with liver disease had significantly higher odds of testing positive for F. hepatica on ELISA than control horses. In 23 sero-positive horses, a range of non-specific clinical signs and blood test abnormalities was reported, with a third of the horses showing no signs. Genotypic analysis of liver flukes from horses provided evidence that these came from the same population as flukes from sheep and cattle.Main limitationsBias could have arisen in the prevalence and case-control studies due to convenience sampling methods, in particular the geographic origin of the horses. Only a small number of horses tested positive so the data on clinical signs are limited.ConclusionsExposure to liver fluke occurs frequently in horses and may be an under-recognised cause of liver disease. Flukes isolated from horses are from the same population as those found in ruminants. When designing and implementing parasite control plans, fluke should be considered, and horses should be tested if appropriate.

Dataset Information

Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis.

Publications

Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis.

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