Abstract
Schistosomiasis is a devastating parasitic disease caused by tremotodes of the genus Schistosoma. Eggs produced by sexually mature schistosomes are the causative agents of for pathogenesis and transmission. Elucidating the molecular mechanism of schistosome development and sexual maturation would facilitate the prevention and control of schistosomiasis. Acetylation of lysine is a dynamic and reversible post-translational modification playing keys role in many biological processes including development in both eukaryotes and prokaryotes. To investigate the impacts of lysine acetylation on Schistosoma japonicum (S. japonicum) development and sexual maturation, we used immunoaffinity-based acetyllysine peptide enrichment combined with mass spectrometry (MS), to perform the first comparative analysis of proteome-wide lysine acetylation in both female and male, juvenile (18 days post infection, 18 dpi) and adult (28 dpi) schistosome samples. In total, we identified 874 unique acetylated sites in 494 acetylated proteins. The four samples shared 47 acetylated sites and 46 proteins. More acetylated sites and proteins shared by both females and males were identified in 28 dpi adults (189 and 143, respectively) than in 18 dpi schistosomula (76 and 59, respectively). More stage-unique acetylated sites and proteins were also identified in 28 dpi adults (494 and 210, respectively) than in 18 dpi schistosomula (73 and 44, respectively). Functional annotation showed that in different developmental stages and genders, a number of proteins involving in muscle movement, glycometabolism, lipid metabolism, energy metabolism, environmental stress resistance, antioxidation, etc., displayed distinct acetylation profiles, which was in accordance with the changes of their biological functions during schistosome development, suggesting that lysine acetylation modification exerted important regulatory roles in schistosome development. Taken together, our data provided the first comparative global survey of lysine acetylation in juvenile and adult S. japonicum, which would deepen our understanding of the molecular mechanism of schistosome development and sexual maturation, and provide clues for the development of new anti-schistosome strategies.
Highlights
Schistosomiasis is one of the most prevalent tropical diseases and remains a major public health problem with approximately 200 million people infected worldwide and around 779 million at the risk of infection (Wang et al, 2008; Cao et al, 2016)
The enriched acetylated peptides were analyzed by LCESI-mass spectrometry (MS)/MS, and the obtained MS/MS spectra were used to search against S. japonicum database with MASCOT search engine (Figure 1A)
We found that in many aspects, both the changes of the transcription profiles and the change of acetylation profiles seemed to be consistent with the physiological and morphological changes during schistosome development. As both the transcriptional regulation and post-translational acetylation has an impact on gene functional output, we propose that the change of a certain biological function at different developmental stages might be the collaborative result of transcriptional regulation and Post-translational modifications (PTM) including acetylation
Summary
Schistosomiasis is one of the most prevalent tropical diseases and remains a major public health problem with approximately 200 million people infected worldwide and around 779 million at the risk of infection (Wang et al, 2008; Cao et al, 2016). Schistosomiasis is a disease caused by the parasitic trematodes of the genus Schistosoma. Schistosomiasis japonica mainly distributed in East Asia, especially in China and the Philippines. Praziquantel (PZQ) is the only effective drug available for treating schistosomiasis, but only effective against adult schistosomes and less effective against juvenile worms. Extensive utilization of PZQ increases the risk of drug resistance (Gonnert and Andrews, 1977; Doenhoff and Pica-Mattoccia, 2006). Development of new anti-schistosome strategies is critical for the control of schistosomiasis
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