Suppression of mRNAs encoding tegument tetraspanins from schistosoma mansoni results in impaired tegument turnover

Tran, Mai H., Freitas, Tori C., Cooper, Leanne, Gaze, Soraya, Gatton, Michelle L., Jones, Malcolm K., Lovas, Erica, Pearce, Edward J., & Loukas, Alex (2010) Suppression of mRNAs encoding tegument tetraspanins from schistosoma mansoni results in impaired tegument turnover. PLoS Pathogens, 6(4), e100084-1.

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Abstract

Schistosomes express a family of integral membrane proteins, called tetraspanins (TSPs), in the outer surface membranes of the tegument. Two of these tetraspanins, Sm-TSP-1 and Sm-TSP-2, confer protection as vaccines in mice, and individuals who are naturally resistant to S. mansoni infection mount a strong IgG response to Sm-TSP-2. To determine their functions in the tegument of S. mansoni we used RNA interference to silence expression of Sm-tsp-1 and Sm-tsp-2 mRNAs. Soaking of parasites in Sm-tsp dsRNAs resulted in 61% (p = 0.009) and 74% (p = 0.009) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in adult worms, and 67%–75% (p = 0.011) and 69%–89% (p = 0.004) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in schistosomula compared to worms treated with irrelevant control (luciferase) dsRNA. Ultrastructural morphology of adult worms treated in vitro with Sm-tsp-2 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Schistosomula exposed in vitro to Sm-tsp-2 dsRNA had a significantly thinner and more vacuolated tegument, and morphology consistent with a failure of tegumentary invaginations to close. Injection of mice with schistosomula that had been electroporated with Sm-tsp-1 and Sm-tsp-2 dsRNAs resulted in 61% (p = 0.005) and 83% (p = 0.002) reductions in the numbers of parasites recovered from the mesenteries four weeks later when compared to dsRNA-treated controls. These results imply that tetraspanins play important structural roles impacting tegument development, maturation or stability.

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ID Code: 75111
Item Type: Journal Article
Refereed: Yes
Keywords: Schistomosa mansoni, tetraspanins, tegument, RNA interference
DOI: 10.1371/journal.ppat.1000840
ISSN: 1553-7374
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Receptors and Membrane Biology (060110)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Public Health & Social Work
Funding:
Copyright Owner: Copyright 2010 Tran et al.
Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Deposited On: 18 Aug 2014 01:37
Last Modified: 18 Aug 2014 23:29

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