The Opisthorchis viverrini genome provides insights into life in the bile duct

doi:10.1038/ncomms5378

. 2014 Jul 9:5:4378.

doi: 10.1038/ncomms5378.

The Opisthorchis viverrini genome provides insights into life in the bile duct

Neil D Young ¹, Niranjan Nagarajan ², Suling Joyce Lin ³, Pasi K Korhonen ⁴, Aaron R Jex ⁴, Ross S Hall ⁴, Helena Safavi-Hemami ⁵, Worasak Kaewkong ⁶, Denis Bertrand ³, Song Gao ⁷, Qihui Seet ³, Sopit Wongkham ⁶, Bin Tean Teh ⁸, Chaisiri Wongkham ⁶, Pewpan Maleewong Intapan ⁹, Wanchai Maleewong ⁹, Xinhua Yang , Min Hu , Zuo Wang , Andreas Hofmann ¹⁰, Paul W Sternberg ¹¹, Patrick Tan ¹², Jun Wang ¹³, Robin B Gasser ⁴

Affiliations

¹ 1] Faculty of Veterinary Science, The University of Melbourne, Melbourne, Victoria 3010, Australia [2].
² 1] Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore [2].
³ Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore.
⁴ Faculty of Veterinary Science, The University of Melbourne, Melbourne, Victoria 3010, Australia.
⁵ Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
⁶ Liver Fluke and Cholangiocarcinoma Research Center, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
⁷ NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 138672, Republic of Singapore.
⁸ Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 138672, Republic of Singapore.
⁹ Research and Diagnostic Center for Emerging Infectious Diseases, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
¹⁰ 1] Faculty of Veterinary Science, The University of Melbourne, Melbourne, Victoria 3010, Australia [2] Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Queensland 4111, Australia.
¹¹ Division of Biology, HHMI, California Institute of Technology, Pasadena, California 91125, USA.
¹² 1] Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore [2] Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 138672, Republic of Singapore.
¹³ 1] [2] Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark [3] Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia [4] Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China.

PMID: 25007141
PMCID: PMC4104445
DOI: 10.1038/ncomms5378

The Opisthorchis viverrini genome provides insights into life in the bile duct

Neil D Young et al. Nat Commun. 2014.

. 2014 Jul 9:5:4378.

doi: 10.1038/ncomms5378.

Authors

Neil D Young ¹, Niranjan Nagarajan ², Suling Joyce Lin ³, Pasi K Korhonen ⁴, Aaron R Jex ⁴, Ross S Hall ⁴, Helena Safavi-Hemami ⁵, Worasak Kaewkong ⁶, Denis Bertrand ³, Song Gao ⁷, Qihui Seet ³, Sopit Wongkham ⁶, Bin Tean Teh ⁸, Chaisiri Wongkham ⁶, Pewpan Maleewong Intapan ⁹, Wanchai Maleewong ⁹, Xinhua Yang , Min Hu , Zuo Wang , Andreas Hofmann ¹⁰, Paul W Sternberg ¹¹, Patrick Tan ¹², Jun Wang ¹³, Robin B Gasser ⁴

Affiliations

¹ 1] Faculty of Veterinary Science, The University of Melbourne, Melbourne, Victoria 3010, Australia [2].
² 1] Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore [2].
³ Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore.
⁴ Faculty of Veterinary Science, The University of Melbourne, Melbourne, Victoria 3010, Australia.
⁵ Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
⁶ Liver Fluke and Cholangiocarcinoma Research Center, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
⁷ NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 138672, Republic of Singapore.
⁸ Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 138672, Republic of Singapore.
⁹ Research and Diagnostic Center for Emerging Infectious Diseases, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
¹⁰ 1] Faculty of Veterinary Science, The University of Melbourne, Melbourne, Victoria 3010, Australia [2] Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Queensland 4111, Australia.
¹¹ Division of Biology, HHMI, California Institute of Technology, Pasadena, California 91125, USA.
¹² 1] Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore [2] Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 138672, Republic of Singapore.
¹³ 1] [2] Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark [3] Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia [4] Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China.

PMID: 25007141
PMCID: PMC4104445
DOI: 10.1038/ncomms5378

Abstract

Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions.

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Figures

Figure 1

Figure 1. Processes proposed to take place during the establishment of Opisthorchis viverrini in the bile duct and the subsequent pathogenesis of biliary disease and associated cholangiocarcinoma.

This proposal integrates salient information from the present study (*) and considers published literature. Metastasis-associated protein 1-mediated fibrosis and transformation of cell cycle progress are linked to: transforming growth factor-beta (TGF-beta) and epidermal growth factor receptor (EGFR)-mediated cell proliferation, associated with an upregulation in Toll-like receptor 4 (TLR4), TGF-beta-stimulated clone 22 homologue (TSC22D1) and EGFR pathway substrate 8 (EPS8); cell cycle activation and cytokinesis associated with an upregulation in dual specificity protein kinase TTK (TTK), serine/threonine kinase 6 (STK6), CDC28 protein kinase regulatory subunit 2 (CKS2), budding uninhibited by benzimidazoles 1 mitotic checkpoint serine/threonine kinase (BUB1 and BUB1B), cell division cycle 20 (CDC20), protein regulator of cytokinesis 1 (PRC1), kinesin family member 2C (KIF2C); and endogenous/exogenous xenobiotic metabolism associated with an upregulation in UDP glucuronosyltransferase 1 family, polypeptide A10 (UGT1A10); UGT 2 family B11 (UGT2B11), carbohydrate sulphotransferase 4 (CHST4) and sulphotransferase family, cytosolic, 1C, member 1 (SULT1C1). Chronic opisthorchiasis is linked to genetic alterations in tumour protein 53 (TP53: 44.4% cases), mothers against decapentaplegic homologue 4 (SMAD4; 16.7%), Kirsten rat sarcoma viral oncogene (KRAS; 16.7%), histone-lysine N-methyltransferase (MLL3; 14.8%), roundabout homologue 2 (ROBO2; 9.3%), guanine nucleotide-binding protein (GNAS; 9.3%) and ring finger protein 43 (RFN43; 9.3%).

Figure 2

Figure 2. Opisthorchis viverrini biological pathways linked to life in the human bile duct.

O. viverrini genes (boxed) associated with responses to environmental stressors or the processing of abundant nutrients found within the bile duct. Genes unique to opisthorchiids (that is, found in O. viverrini and Clonorchis sinensis) or gene families, which have expanded within this group of flukes are shown in red. Pathways required for the degradation and uptake of micelles, including very-low (VLDL), low (LDL), intermediate (IDL) and high density lipoproteins (HDL), are represented by blue arrows.

Figure 3

Figure 3. Opisthorchis viverrini and Clonorchis sinensis proteins with at least one granulin domain.

(a) Alignment of the amino acid sequences translated from O. viverrini and C. sinensis protein-coding regions of putative progranulin (PGRN) and granulin (GRN-1 and GRN-2) genes, displaying the structural organization of the signal peptide and cysteine-rich granulin domain/s (InterProScan ID: IPR000118). Conserved granulin domain residues are highlighted in yellow. (b) Amino acid logos of conserved granulin domains encoded within O. viverrini and C. sinensis granulins (GRN-1 and GRN-2; one granulin domain each), PGRN (eight domains per protein) and human PGRN (seven granulin domains). Logo is coloured on the basis of amino acid chemistry, where amino acid residues are grouped by colour, depending on their chemical characteristics, so that polar residues (G, S, T, Y and C) are green, neutral (Q and N) are purple, basic (K, R and H) are blue, acidic (D and E) are red and hydrophobic (A, V, L, I, P, W, F and M) are black. Residue height denotes the measure of uncertainty for each residue (in bits per symbol). (c) Alignment of the predicted mature opisthorchiid-specific granulin proteins.

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References

1. World Health Organization. The World Health Report: Changing History 1–96World Health Organization (2004).
1. Keiser J. & Utzinger J. Food-borne trematodiases. Clin. Microbiol. Rev. 22, 466–483 (2009). - PMC - PubMed
1. Bouvard V. et al. A review of human carcinogens-Part B: biological agents. Lancet Oncol. 10, 321–322 (2009). - PubMed
1. Khan S. A., Toledano M. B. & Taylor-Robinson S. D. Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB (Oxford) 10, 77–82 (2008). - PMC - PubMed
1. Parkin D. M. The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer 118, 3030–3044 (2006). - PubMed

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[1] World Health Organization. The World Health Report: Changing History 1–96World Health Organization (2004).

[2] World Health Organization. The World Health Report: Changing History 1–96World Health Organization (2004).

[3] Keiser J. & Utzinger J. Food-borne trematodiases. Clin. Microbiol. Rev. 22, 466–483 (2009). - PMC - PubMed

[4] Keiser J. & Utzinger J. Food-borne trematodiases. Clin. Microbiol. Rev. 22, 466–483 (2009). - PMC - PubMed

[5] Bouvard V. et al. A review of human carcinogens-Part B: biological agents. Lancet Oncol. 10, 321–322 (2009). - PubMed

[6] Bouvard V. et al. A review of human carcinogens-Part B: biological agents. Lancet Oncol. 10, 321–322 (2009). - PubMed

[7] Khan S. A., Toledano M. B. & Taylor-Robinson S. D. Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB (Oxford) 10, 77–82 (2008). - PMC - PubMed

[8] Khan S. A., Toledano M. B. & Taylor-Robinson S. D. Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB (Oxford) 10, 77–82 (2008). - PMC - PubMed

[9] Parkin D. M. The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer 118, 3030–3044 (2006). - PubMed

[10] Parkin D. M. The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer 118, 3030–3044 (2006). - PubMed

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The Opisthorchis viverrini genome provides insights into life in the bile duct

Affiliations

The Opisthorchis viverrini genome provides insights into life in the bile duct

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous