Suppression of mRNAs Encoding Tegument Tetraspanins from Schistosoma mansoni Results in Impaired Tegument Turnover

PLoS Pathogens

Leanne Cooper¹  Tori C. Freitas¹  Soraya Gaze²  Mai H. Tran²  Michelle L. Gatton²  Erica Lovas²  Malcolm K. Jones²  Edward J. Pearce³  Alex Loukas³ 

[1] Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Division of Infectious Diseases, Queensland Institute of Medical Research, Brisbane, Queensland, Australia;School of Veterinary Sciences, The University of Queensland, Brisbane, Queensland, Australia

关键词: Schistosoma mansoni;    Schistosoma;    Parasitic diseases;    RNA interference;    Luciferase;    Cell membranes;    Messenger RNA;    Tegument proteins;   

DOI  :  10.1371/journal.ppat.1000840

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY