The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini

Mulvenna, Jason, Sripa, Banchob, Brindley, Paul J., Gorman, Jeffrey, Jones, Malcolm K., Colgrave, Michelle L., Jones, Alun, Nawaratna, Sujeevi, Laha, Thewarach, Suttiprapa, Sutas, Smout, Michael J., and Loukas, Alex (2010) The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini. Proteomics, 10 (5). pp. 1063-1078.

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Abstract

Infection with the human liver fluke, Opisthorchis viverrini, is a serious public health problem in Thailand, Laos and nearby locations in Southeast Asia. Both experimental and epidemiological evidence strongly implicate liver fluke infection in the etiology of one of the liver cancer subtypes, cholangiocarcinoma (CCA). To identify parasite proteins critical for liver fluke survival and the etiology of CCA, OFFGEL electrophoresis and multiple reaction monitoring were employed to characterize 300 parasite proteins from the O. viverrini excretory/secretory products and, utilizing selective labeling and sequential solubilization, from the host-exposed tegument. The excretory/secretory included a complex mixture of proteins that have been associated with cancers, including proteases of different mechanistic classes and orthologues of mammalian growth factors and anti-apoptotic proteins. Also identified was a cysteine protease inhibitor which, in other helminth pathogens, induces nitric oxide production by macrophages, and, hence may contribute to malignant transformation of inflamed cells. More than 160 tegumental proteins were identified using sequential solubilization of isolated teguments, and a subset of these was localized to the surface membrane of the tegument by labeling living flukes with biotin and confirming surface localization with fluorescence microscopy. These included annexins, which are potential immuno-modulators, and orthologues of the schistosomiasis vaccine antigens Sm29 and tetraspanin-2. Novel roles in pathogenesis were suggested for the tegument-host interface since more than ten surface proteins had no homologues in the public databases. The O. viverrini proteins identified here provide an extensive catalogue of novel leads for research on the pathogenesis of opisthorchiasis and the development of novel interventions for this disease and CCA, as well as providing a scaffold for sequencing the genome of this fluke.

Item ID: 28507
Item Type: Article (Research - C1)
ISSN: 1615-9861
Keywords: animal proteomics; biotinylation; cholangiocarcinoma; Opisthorchis viverrini; tegument
Funders: National Institute of Allergy and Infectious Disease (NIAID), Thailand-Tropical Diseases Research Program
Projects and Grants: UO1AI065871, ID02-2-HEL-05-054
Date Deposited: 19 Aug 2013 02:17
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 30%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060108 Protein Trafficking @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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