Tetraspanin-2 localisation in high pressure frozen and freeze-substituted Schistosoma mansoni adult males reveals its distribution in membranes of tegumentary vesicles

Schulte, Leigh; Lovas, Erica; Green, Kathryn; Mulvenna, Jason; Gobert, Geoffrey N.; Morgan, Garry; Jones, Malcolm K.

doi:10.1016/j.ijpara.2013.04.003

Cited by 19 publications

(19 citation statements)

References 38 publications

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“…In fact, the tegument of digeneans, such as schistosomes, due to its very high metabolic activity, represents a very sensitive target for examining the effects of anthelmintic drugs upon the parasite. It is also worth noting that, according to the recent studies on the concept of vaccination, the most efficacious schistosome vaccines are directed against tegumental structures (Schulte et al 2013), which opens up a new way of looking at the tegument.…”

Section: Discussionmentioning

confidence: 99%

A transmission electron microscopical study of the tegument of Maritrema feliui (Digenea: Microphallidae)

Świderski

Montoliu

Feliú

et al. 2013

Acta Parasitologica

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The tegument of the microphallid digenean Maritrema feliui, examined by means of TEM, is described as a syncytial epithelium organised into two layers. The outer layer is an external anucleate, cytoplasmic region connected to a second region composed of nucleate perikarya (cytons) deeply embedded in the surrounding cortical parenchyma. The surface layer of the tegument is covered by a plasma membrane with many deep invaginations, which are apparently pinocytotic. This layer also bears numerous large, electron-dense spines of two types, which are intracellular and attached to the basal plasma membrane. Its cytoplasm is rich in free ribosomes, contains numerous mitochondria, disc-shaped granules frequently arranged in a rouleau, and several large, moderately electron-dense, membranous bodies. The subtegumentary perikarya and their nuclei, which are both flattened, are described in detail, as are their connections with the surface tegument. These perikarya appear to be the source of the disc-shaped granules and some of the other inclusions present in the surface layer. The main characteristics of the tegumental structure of M. feliui are commented upon in relation to the findings of previous publications and their suggested functions.

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Section: Discussionmentioning

confidence: 99%

A transmission electron microscopical study of the tegument of Maritrema feliui (Digenea: Microphallidae)

Świderski

Montoliu

Feliú

et al. 2013

Acta Parasitologica

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“…According to models of the S. mansoni tegument, the primary vaccine target Sm-TSP-2 (tetraspanin-2) occurs in the plasma membrane, that is, it lies hidden from the host under the membranocalyx (Wilson, 2012). Recent immunolocalization data suggest the molecule is even more hidden from the host, in adult parasites at least, occurring predominantly in association with surface invaginations of the hosts and in subsidiary membranes (Schulte et al, 2013).…”

Section: Tegument Proteins As Vaccine Targetsmentioning

confidence: 99%

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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“…Combined with cell and immuno-biological investigation, [11,12] next-generation sequencing and transcriptomics methodologies, [13] advanced modelling approaches [14] and the probing of key proteins with small molecules, [15] crystallography continues to provide the crucial information for rationale and target discovery. Members of the genus Schistosoma pathogenic flatworms are responsible for chronic infections throughout Africa and many parts of the world.…”

Section: Structures Of Parasite Proteinsmentioning

confidence: 99%

The Relevance of Structural Biology in Studying Molecules Involved in Parasite–Host Interactions: Potential for Designing New Interventions

et al. 2014

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1Mason et al. Structures of parasite proteinsNew interventions against infectious diseases require a detailed knowledge and understanding of pathogen-host interactions and pathogeneses at the molecular level. The combination of the considerable advances in systems biology research with methods to explore the structural biology of molecules is poised to provide new insights into these areas. Importantly, exploring threedimensional structures of proteins is central to understanding disease processes, and establishing structure-function relationships assists in identification and assessment of new drug and vaccine targets. Frequently, the molecular arsenal deployed by invading pathogens, and in particular parasites, reveals a common theme whereby families of proteins with conserved three-dimensional folds play crucial roles in infectious processes, but individual members of such families show high levels of specialisation which is often achieved through grafting particular structural features onto the shared overall fold. Accordingly, the applicability of predictive methodologies based on the primary structure of proteins or genome annotations is limited, particularly when thorough knowledge of molecular level mechanisms is required. Such instances exemplify the need for experimental threedimensional structures provided by protein crystallography, which remain an essential component of this area of research. In the present article, we review two examples of key protein families recently investigated in our laboratories, which could represent intervention targets in the metabolome or secretome of parasites. IntroductionInfectious diseases caused by eukaryotic pathogens represent a major disease burden to humans world-wide. In the absence of effective preventative approaches and new intervention strategies, this burden is likely to increase further, [1,2] compounded by food and water shortages, economic crises, wars and climate change, particularly in disadvantaged countries. In addition, there is evidence of increasing problems with resistance in pathogens against a broad range of chemotherapeutic agents, compromising the treatment of infectious diseases. [3] Moreover, in spite of major efforts, there are very few examples of success in developing new drugs and vaccines against eukaryotic pathogens, [4,5] indicating that alternative methods are needed at a time of major advances in molecular and computer technologies. In our opinion, the development of new treatments requires a detailed understanding of pathogens, host interactions and the molecular processes of disease. For instance, knowledge of the three-dimensional structures of proteins with pivotal roles in disease, and the probing of their underlying biology are crucial for understanding the pathogenesis. Through establishing the relevant structure-function relationships, one can elucidate how individual proteins function, so that new ways of disrupting relevant pathways can be found, in order to facilitate the identification of new drug and vaccine targets. ...

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Tetraspanin-2 localisation in high pressure frozen and freeze-substituted Schistosoma mansoni adult males reveals its distribution in membranes of tegumentary vesicles

Cited by 19 publications

References 38 publications

A transmission electron microscopical study of the tegument of Maritrema feliui (Digenea: Microphallidae)

A transmission electron microscopical study of the tegument of Maritrema feliui (Digenea: Microphallidae)

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

The Relevance of Structural Biology in Studying Molecules Involved in Parasite–Host Interactions: Potential for Designing New Interventions

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