Exposed proteins of the Schistosoma japonicum tegument

Mulvenna, Jason; Moertel, Luke; Jones, Malcolm K.; Nawaratna, Sujeevi; Lovas, Erica; Gobert, Geoffrey N.; Colgrave, Michelle L.; Jones, Alun; Loukas, Alex; McManus, Donald P.

doi:10.1016/j.ijpara.2009.10.002

Cited by 141 publications

(149 citation statements)

References 68 publications

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“…As stated, Sm-Anx-B7a, B22 and B30 are distinctly associated with the syncytial tegument (Braschi and Wilson, 2006;Mulvenna et al, 2010). Our tissue-specific transcriptomic survey of female S. japonicum indicated that different annexins were expressed preferentially by different cell types, with the gut lining expressing annexin B7 and B22, while the vitelline gland expressed annexin B5 (Gobert et al, 2009a).…”

Section: Schistosome Annexinssupporting

confidence: 54%

“…Analysis of the schistosome proteome has vastly increased the speed of identification of tegument proteins (Braschi and Wilson, 2006;Mulvenna et al, 2010;Castro-Borges et al, 2011;Jia et al, 2014) (Table 1). A series of experiments have allowed different proteins to be assigned to the distinct membrane fractions of the apical membrane complex (Wilson, 2012), although these assignments are likely to be crude and require further analysis by refined localization tools.…”

Section: Figurementioning

confidence: 99%

“…A series of experiments have allowed different proteins to be assigned to the distinct membrane fractions of the apical membrane complex (Wilson, 2012), although these assignments are likely to be crude and require further analysis by refined localization tools. A range of molecules has been identified including glucose transporters, proteases and other enzymes, receptors, chaperones and structural proteins (Mulvenna et al, 2010;Castro-Borges et al, 2011;Wilson, 2012). Further confirmation of the co-location of many of these molecules has come from interaction studies of Sm-TSP-2 (Jia et al, 2014), which show strong interactions, as stated, with a range of surface-linked molecules including annexin B30, alkaline phosphatase, actin, an aldolase, calpain, HSP70, dysferlin and Sm29, a schistosome-specific molecule.…”

Section: Figurementioning

confidence: 99%

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Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

Leow

Willis

Hofmann

et al. 2014

British J Pharmacology

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Neglected tropical diseases are a group of some 17 diseases that afflict poor and predominantly rural people in developing nations. One significant disease that contributes to substantial morbidity in endemic areas is schistosomiasis, caused by infection with one of five species of blood fluke belonging to the trematode genus Schistosoma. Although there is one drug available for treatment of affected individuals in clinics, or for mass administration in endemic regions, there is a need for new therapies. A prominent target organ of schistosomes, either for drug or vaccine development, is the peculiar epithelial syncytium that forms the body wall (tegument) of this parasite. This dynamic layer is maintained and organized by concerted activity of a range of proteins, among which are the abundant tegumentary annexins. In this review, we will outline advances in structure-function analyses of these annexins, as a means to understanding tegument cell biology in host-parasite interaction and their potential exploitation as targets for anti-schistosomiasis therapies. LINKED ARTICLESThis article is part of a themed section on Annexins VII Programme. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2015.172.issue-7 Abbreviations Anx, annexin; NTDs, neglected tropical diseases; RA, radiation attenuated; Sm, Schistosoma mansoni; TEMs, tetraspanin-enriched microdomains; TSP, tetraspanin Neglected tropical diseases (NTDs)NTDs include some 17 lesser known chronic infections that affect poor and disenfranchised people, primarily, but not exclusively, in developing nations (Hotez et al., 2007;Hotez and Fenwick, 2009). Chronic infections caused by NTDs lead to many adverse outcomes in affected populations and contribute substantially to human morbidity. In addition to microbial and protozoan diseases, NTDs include a number of helminth infections, such as diseases caused by flatworm parasites, notably schistosomiasis, echinococcosis and liver fluke diseases, as well as roundworm parasites, such as the major soil transmitted helminth infections (ascariasis, trichuriasis and hookworm diseases). Although no individual NTD rivals the major infectious threats of HIV, malaria or tuberculosis in terms of global impact of disease, collectively, the NTDs contribute substantially to morbidity throughout the world (Engels and Savioli, 2006). A number of factors present major challenges for the development of new treatments for NTDs. Firstly, NTDs are chronic diseases, which may reside in affected people as lifelong infections. Secondly, NTDs are not always associated with human mortality and the burden of these diseases can be subtle, hidden among such other measures of disease burden as hindered development, poor cognitive function and chronic ailments. Thirdly, as stated, NTDs often affect the poorest of the poor, people often unable to pay for medical treatments, especially for chronic illnesses. Hence, these diseases receive less attention than other, immediately lifethreatening infectious diseases. La...

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Section: Schistosome Annexinssupporting

confidence: 54%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

Leow

Willis

Hofmann

et al. 2014

British J Pharmacology

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“…Positive immunoreactivity was also detected in regions subjacent to the surface layer (arrowheads), reflecting the presence of biotin in interconnecting bridges, and in discrete regions in sub-muscle cells (long arrows), likely to be tegumentary cytons. Figure modified and reproduced with permission from Mulvenna et al, 2010. lysozyme-like proteins, and transthyretin-like proteins, all of which are vaccine candidates but have yet to be assessed for efficacy in animal models.…”

Section: Figmentioning

confidence: 99%

Vaccinomics for the Major Blood Feeding Helminths of Humans

Loukas

Gaze

Mulvenna

et al. 2011

OMICS: A Journal of Integrative Biology

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Approximately one billion people are infected with hookworms and/or blood flukes (schistosomes) in developing countries. These two parasites are responsible for more disability adjusted life years lost than most other neglected tropical diseases (NTDs), and together, are second only to malaria. Although anthelmintic drugs are effective and widely available, they do not protect against reinfection, resistant parasites are likely to emerge, and mass drug administration programs are unsustainable. Therefore, there is a pressing need for the development of vaccines against these parasites. In recent years, there have been major advances in our understanding of hookworms and schistosomes at the molecular level through the use of ''omics'' technologies. The secretomes of these parasites have been characterized using transcriptomics, genomics, proteomics, and newly developed gene manipulation and silencing techniques, and the proteins of interest are now the target of novel antigen discovery approaches, notably immunomics. This research has resulted in the discovery, development, and early stage clinical trials of subunit vaccines against hookworms and schistosomes.

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“…An examination of the proteins identified in the cross-linking experiments (Table 2) shows that half have been previously identified at the surface of S. mansoni using membrane-impermeable biotin labeling (38) and, on the evidence presented here, are potential members of the exposed TEM in schistosomes. Of the remaining proteins, whereas calpain and HSP70 have been putatively identified as membraneassociated in S. mansoni (38) and S. japonicum (39), the presence of both actin and fructose-bisphosphate aldolase suggests vertical interactions were also captured. Although BS3 is membrane-impermeable, limited penetration of the membranocalyx and/or plasma membrane could have occurred across damaged membranes or by active transport.…”

Section: Table 2 Potential Members Of Sm-tsp-2 Mediated Temsmentioning

confidence: 99%

Solution Structure, Membrane Interactions, and Protein Binding Partners of the Tetraspanin Sm-TSP-2, a Vaccine Antigen from the Human Blood Fluke Schistosoma mansoni

Jia

Schulte

Loukas

et al. 2014

Journal of Biological Chemistry

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Background: Schistosome tetraspanin Sm-TSP-2 is a vaccine antigen. Results: We describe the structure of the large extracellular domain of Sm-TSP-2, develop a model of its interactions with Tetraspanin-enriched-microdomain proteins and plasma membrane, and identify TEM constituents. Conclusion: Structural conservation of the domain means this model is likely applicable to TSPs in general.Significance: Tetraspanin-enriched-microdomain proteins provide further targets for multiplex vaccines and/or novel drug targets.

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Exposed proteins of the Schistosoma japonicum tegument

Cited by 141 publications

References 68 publications

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

Vaccinomics for the Major Blood Feeding Helminths of Humans

Solution Structure, Membrane Interactions, and Protein Binding Partners of the Tetraspanin Sm-TSP-2, a Vaccine Antigen from the Human Blood Fluke Schistosoma mansoni

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