Epigenetic Changes Modulate Schistosome Egg Formation and Are a Novel Target for Reducing Transmission of Schistosomiasis
Schistosoma mansoni is a parasitic worm that causes schistosomiasis, a debilitating disease in Africa and South America. Female worms mated with males produce hundreds of eggs that can reach the environment to propagate the biological cycle, or become trapped in host tissues, triggering inflammation and pathology. Because eggshell formation is a key step in egg development and viability, we have studied the molecular mechanisms of S. mansoni eggshell development, focusing on a major eggshell gene, Smp14. Using a variety of technical and biological approaches, we obtained strong evidence that eggshell formation depends on nuclear receptors and coactivators with chromatin modifying activities, mainly histone acetylation. Inhibition or partial deletion of S. mansoni histone acetyltransferases impaired the expression of Smp14, culminating in a severe negative effect on eggshell formation. Our findings will contribute not only to a better understanding of sex and tissue-specific gene regulation in S. mansoni but also provide an alternative strategy for interfering with the egg production, which might be targeted in novel therapeutics directed against this parasite.
Vyšlo v časopise:
Epigenetic Changes Modulate Schistosome Egg Formation and Are a Novel Target for Reducing Transmission of Schistosomiasis. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004116
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004116
Souhrn
Schistosoma mansoni is a parasitic worm that causes schistosomiasis, a debilitating disease in Africa and South America. Female worms mated with males produce hundreds of eggs that can reach the environment to propagate the biological cycle, or become trapped in host tissues, triggering inflammation and pathology. Because eggshell formation is a key step in egg development and viability, we have studied the molecular mechanisms of S. mansoni eggshell development, focusing on a major eggshell gene, Smp14. Using a variety of technical and biological approaches, we obtained strong evidence that eggshell formation depends on nuclear receptors and coactivators with chromatin modifying activities, mainly histone acetylation. Inhibition or partial deletion of S. mansoni histone acetyltransferases impaired the expression of Smp14, culminating in a severe negative effect on eggshell formation. Our findings will contribute not only to a better understanding of sex and tissue-specific gene regulation in S. mansoni but also provide an alternative strategy for interfering with the egg production, which might be targeted in novel therapeutics directed against this parasite.
Zdroje
1. KingCH, Dangerfield-ChaM (2008) The unacknowledged impact of chronic schistosomiasis. Chronic Illn 4: 65–79.
2. CioliD, BassoA, ValleC, Pica-MattocciaL (2012) Decades down the line: the viability of praziquantel for future schistosomiasis treatment. Expert Rev Anti Infect Ther 10: 835–837.
3. PearceEJ, MacDonaldAS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2: 499–511.
4. deWalickS, TielensAG, van HellemondJJ (2012) Schistosoma mansoni: the egg, biosynthesis of the shell and interaction with the host. Exp Parasitol 132: 7–13.
5. BobekL, RekoshDM, van KeulenH, LoVerdePT (1986) Characterization of a female-specific cDNA derived from a developmentally regulated mRNA in the human blood fluke Schistosoma mansoni. Proc Natl Acad Sci U S A 83: 5544–5548.
6. KosterB, DargatzH, SchroderJ, HirzmannJ, HaarmannC, et al. (1988) Identification and localisation of the products of a putative eggshell precursor gene in the vitellarium of Schistosoma mansoni. Mol Biochem Parasitol 31: 183–198.
7. KunzW, OpatzK, FinkenM, SymmonsP (1987) Sequences of two genomic fragments containing an identical coding region for a putative egg-shell precursor protein of Schistosoma mansoni. Nucleic Acids Res 15: 5894.
8. ChenLL, RekoshDM, LoVerdePT (1992) Schistosoma mansoni p48 eggshell protein gene: characterization, developmentally regulated expression and comparison to the p14 eggshell protein gene. Mol Biochem Parasitol 52: 39–52.
9. de Moraes MacielR, de Silva DutraDL, RumjanekFD, JulianoL, JulianoMA, et al. (2004) Schistosoma mansoni histone acetyltransferase GCN5: linking histone acetylation to gene activation. Mol Biochem Parasitol 133: 131–135.
10. MansureJJ, FurtadoDR, de OliveiraFM, RumjanekFD, FrancoGR, et al. (2005) Cloning of a protein arginine methyltransferase PRMT1 homologue from Schistosoma mansoni: evidence for roles in nuclear receptor signaling and RNA metabolism. Biochem Biophys Res Commun 335: 1163–1172.
11. BertinB, OgerF, CornetteJ, CabyS, NoelC, et al. (2006) Schistosoma mansoni CBP/p300 has a conserved domain structure and interacts functionally with the nuclear receptor SmFtz-F1. Mol Biochem Parasitol 146: 180–191.
12. de Moraes MacielR, da CostaRF, de OliveiraFM, RumjanekFD, FantappieMR (2008) Protein acetylation sites mediated by Schistosoma mansoni GCN5. Biochem Biophys Res Commun 370: 53–56.
13. FantappieMR, Bastos de OliveiraFM, de Moraes MacielR, RumjanekFD, WuW, et al. (2008) Cloning of SmNCoA-62, a novel nuclear receptor co-activator from Schistosoma mansoni: assembly of a complex with a SmRXR1/SmNR1 heterodimer, SmGCN5 and SmCBP1. Int J Parasitol 38: 1133–1147.
14. FantappieMR, FurtadoDR, RumjanekFD, LoverdePT (2008) A unique nuclear receptor direct repeat 17 (DR17) is present within the upstream region of Schistosoma mansoni female-specific p14 gene. Biochem Biophys Res Commun 371: 689–693.
15. FurdasSD, ShekfehS, BissingerEM, WagnerJM, SchlimmeS, et al. (2011) Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors. Bioorg Med Chem 19: 3678–3689.
16. GalantiSE, HuangSC, PearceEJ (2012) Cell death and reproductive regression in female Schistosoma mansoni. PLoS Negl Trop Dis 6: e1509.
17. PerissiV, RosenfeldMG (2005) Controlling nuclear receptors: the circular logic of cofactor cycles. Nat Rev Mol Cell Biol 6: 542–554.
18. KatoS, YokoyamaA, FujikiR (2011) Nuclear receptor coregulators merge transcriptional coregulation with epigenetic regulation. Trends Biochem Sci 36: 272–281.
19. FitzpatrickJM, HiraiY, HiraiH, HoffmannKF (2007) Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinases. FASEB J 21: 823–835.
20. NevesRH, de Lamare BiolchiniC, Machado-SilvaJR, CarvalhoJJ, BranquinhoTB, et al. (2005) A new description of the reproductive system of Schistosoma mansoni (Trematoda: Schistosomatidae) analyzed by confocal laser scanning microscopy. Parasitol Res 95: 43–49.
21. HotezPJ, KamathA (2009) Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden. PLoS Negl Trop Dis 3: e412.
22. FenwickA, WebsterJP, Bosque-OlivaE, BlairL, FlemingFM, et al. (2009) The Schistosomiasis Control Initiative (SCI): rationale, development and implementation from 2002–2008. Parasitology 136: 1719–1730.
23. ArrowsmithCH, BountraC, FishPV, LeeK, SchapiraM (2012) Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 11: 384–400.
24. EbersbergerI, KnoblochJ, KunzW (2005) Cracks in the shell–zooming in on eggshell formation in the human parasite Schistosoma mansoni. Dev Genes Evol 215: 261–267.
25. CuiL, MiaoJ, FuruyaT, FanQ, LiX, et al. (2008) Histone acetyltransferase inhibitor anacardic acid causes changes in global gene expression during in vitro Plasmodium falciparum development. Eukaryot Cell 7: 1200–1210.
26. VanagasL, JeffersV, BogadoSS, DalmassoMC, SullivanWJJr, et al. (2012) Toxoplasma histone acetylation remodelers as novel drug targets. Expert Rev Anti Infect Ther 10: 1189–1201.
27. DuboisF, CabyS, OgerF, CosseauC, CapronM, et al. (2009) Histone deacetylase inhibitors induce apoptosis, histone hyperacetylation and up-regulation of gene transcription in Schistosoma mansoni. Mol Biochem Parasitol 168: 7–15.
28. LancelotJ, CabyS, Dubois-AbdesselemF, VanderstraeteM, TroletJ, et al. (2013) Schistosoma mansoni Sirtuins: characterization and potential as chemotherapeutic targets. PLoS Negl Trop Dis 7: e2428.
29. MarekM, KannanS, HauserAT, Moraes MouraoM, CabyS, et al. (2013) Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key epigenetic player in the blood fluke Schistosoma mansoni. PLoS Pathog 9: e1003645.
30. PierceRJ, Dubois-AbdesselemF, LancelotJ, AndradeL, OliveiraG (2012) Targeting schistosome histone modifying enzymes for drug development. Curr Pharm Des 18: 3567–3578.
31. YorkB, O'MalleyBW (2010) Steroid receptor coactivator (SRC) family: masters of systems biology. J Biol Chem 285: 38743–38750.
32. SmythJD, CleggJA (1959) Egg-shell formation in trematodes and cestodes. Exp Parasitol 8: 286–323.
33. KnoblochJ, KunzW, GreveldingCG (2006) Herbimycin A suppresses mitotic activity and egg production of female Schistosoma mansoni. Int J Parasitol 36: 1261–1272.
34. HuangSC, FreitasTC, AmielE, EvertsB, PearceEL, et al. (2012) Fatty acid oxidation is essential for egg production by the parasitic flatworm Schistosoma mansoni. PLoS Pathog 8: e1002996.
35. BuroC, OliveiraKC, LuZ, LeutnerS, BeckmannS, et al. (2013) Transcriptome analyses of inhibitor-treated schistosome females provide evidence for cooperating Src-kinase and TGFbeta receptor pathways controlling mitosis and eggshell formation. PLoS Pathog 9: e1003448.
36. DebloisG, GiguereV (2003) Ligand-independent coactivation of ERalpha AF-1 by steroid receptor RNA activator (SRA) via MAPK activation. J Steroid Biochem Mol Biol 85: 123–131.
37. WilliamsCC, BasuA, El-GharbawyA, CarrierLM, SmithCL, et al. (2009) Identification of four novel phosphorylation sites in estrogen receptor alpha: impact on receptor-dependent gene expression and phosphorylation by protein kinase CK2. BMC Biochem 10: 36.
38. SmithersSR, TerryRJ (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology 55: 695–700.
39. BeckmannS, QuackT, DissousC, CailliauK, LangG, et al. (2012) Discovery of platyhelminth-specific alpha/beta-integrin families and evidence for their role in reproduction in Schistosoma mansoni. PLoS One 7: e52519.
40. CabyS, PierceRJ (2009) Quantitative chromatin immunoprecipitation (Q-ChIP) applied to Schistosoma mansoni. Mol Biochem Parasitol 166: 77–80.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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