Background
The three epidemiologically important Opisthorchiidae liver flukes
Opisthorchis felineus
,
O. viverrini
, and
Clonorchis sinensis
, are believed to harbour similar potencies to provoke hepatobiliary diseases in their definitive hosts, although their populations have substantially different ecogeographical aspects including habitat, preferred hosts, population structure. Lack of
O. felineus
genomic data is an obstacle to the development of comparative molecular biological approaches necessary to obtain new knowledge about the biology of Opisthorchiidae trematodes, to identify essential pathways linked to parasite-host interaction, to predict genes that contribute to liver fluke pathogenesis and for the effective prevention and control of the disease.
Results
Here we present the first draft genome assembly of
O. felineus
and its gene repertoire accompanied by a comparative analysis with that of
O. viverrini
and
Clonorchis sinensis
. We observed both noticeably high heterozygosity of the sequenced individual and substantial genetic diversity in a pooled sample. This indicates that potency of
O. felineus
population for rapid adaptive response to control and preventive measures of opisthorchiasis is higher than in
O. viverrini
and
C. sinensis
. We also have found that all three species are characterized by more intensive involvement of trans-splicing in RNA processing compared to other trematodes.
Conclusion
All revealed peculiarities of structural organization of genomes are of extreme importance for a proper description of genes and their products in these parasitic species. This should be taken into account both in academic and applied research of epidemiologically important liver flukes. Further comparative genomics studies of liver flukes and non-carcinogenic flatworms allow for generation of well-grounded hypotheses on the mechanisms underlying development of cholangiocarcinoma associated with opisthorchiasis and clonorchiasis as well as species-specific mechanisms of these diseases.
Electronic supplementary material
The online version of this article (10.1186/s12864-019-5752-8) contains supplementary material, which is available to authorized users.
Opisthorchiasis caused by food-borne trematode
Opisthorchis felineus
is a substantial public health problem, with 17 million persons infected worldwide. This chronic disease is associated with hepatobiliary inflammation, cholangiocyte dysplasia, cholangiofibrosis, intraepithelial neoplasia, and even cholangiocarcinoma among chronically infected individuals. To provide first insights into the mechanism by which
O
.
felineus
infection causes precancerous liver lesions, we investigated the level of oxidative stress (lipid peroxidation byproducts and 8-hydroxy-2′-deoxyguanosine) as well as the time course profiles of chronic inflammation and fibrogenesis markers in the dynamics of opisthorchiasis from 1 month to 1.5 years postinfection in an experimental model based on golden hamsters
Mesocricetus auratus
. For the first time, we showed that
O
.
felineus
infection provokes time-dependent accumulation of oxidative hepatobiliary lesions in the injured liver of hamsters. In particular, over the course of infection, lipid peroxidation byproducts 4-hydroxynonenal and malondialdehyde were upregulated; these changes in general correlate with the dynamics of hepatic histopathological changes. We detected macrophages with various immunophenotypes and elevated levels of CD68, COX2, and CD163 in the
O
.
felineus
–infected animals. Meanwhile, there was direct time-dependent elevation of TNF-α (R = 0.79; p < 0.001) and CD163 protein levels (R = 0.58; p = 0.022). We also provide quantitative data about epithelial hyperplasia marker CK7 and a marker of myofibroblast activation (α smooth muscle actin). Our present data provide first insights into the histopathological mechanism by which
O
.
felineus
infection causes liver injuries. These findings support the inclusion of
O
.
felineus
in Group 1 of biological carcinogens.
Opisthorchosis is a helminthiasis affecting mainly the hepatobiliary system and pancreas; its most dramatic complication is malignization of the organs infected by the parasites. The causative agents of opisthorchosis are two species of liver flukes, the trematodes belonging to the family Opisthorchiidae--Opisthorchis felineus and O. viverrini. The Chinese liver fluke, Clonorchis sinensis, also member of the family Opisthorchiidae, causes clonorchosis, a disease very close in symptomatology. According to different estimations, up to 40 million people are currently infected with these liver flukes and up to 600-750 million people in Eurasian countries constitute the risk group. These parasites colonize ever-increasing new areas in Eurasia where this disease has never been previously reported. Opisthorchiases are gradually transforming from a local problem of individual geographic regions to a widespead problem; in particular, O. viverrini is now referred to as "an underestimated parasite." As we see it, O. felineus has all the reasons to share this status. First and foremost, the observed expansion is likely to be connected with the ever-increasing intensity of traffic flows and migration of the infection carriers between cities, regions, and countries. This review briefs the characteristics of O. felineus and the other liver flukes persisting in various countries of Eurasia, clinical manifestations of opisthorchosis, the drugs for chemotherapy of trematodiasis, and the strategy for discovery of new antihelminthic drugs.
The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.
Helicobacter pylori causes a wide range of human diseases including cancer. Carcinogenic foodborne trematodes Opisthorchis viverrini, Clonorchis sinensis, and O. felineus might promote transmission and spread of H. pylori infection in the definitive mammalian host, which in turn might contribute to the liver fluke-associated malignancy. Our objectives were to find out whether liver flukes O. felineus, O. viverrini, and C. sinensis are carriers of Helicobacter pylori and to determine whether H. pylori is present in feces, bile, and stomach samples from the experimentally infected hamsters. We found that liver flukes are not reservoirs of H. pylori. Nevertheless, the prevalence of H. pylori and the H. pylori ureA gene copy number were significantly elevated after the infection. Overall, although the liver flukes O. felineus, C. sinensis, and O. viverrini are not reservoirs of H. pylori, the infection with the liver flukes significantly modifies the biliary and gut microbiota by increasing H. pylori abundance. This may be a feature of any liver fluke pathogenesis that have not previously been taken into account. Our findings appear to be novel in terms of comparative assessment of the host microbiota and Helicobacter abundance during epidemiologically important liver fluke infections.
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