Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni
Schistosoma mansoni is a parasitic plathyhelminth responsible for intestinal schistosomiasis (or bilharziasis), a disease affecting 67 million people worldwide and causing an important economic burden. The schistosomicides hycanthone, and its later proxy oxamniquine, were widely used for treatments...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00207/full |
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| author | David eRoquis David eRoquis Julie MJ Lepesant Julie MJ Lepesant Emanuel eVillafan Emanuel eVillafan Cristina eVieira Céline eCosseau Céline eCosseau Christoph eGrunau Christoph eGrunau |
| author_facet | David eRoquis David eRoquis Julie MJ Lepesant Julie MJ Lepesant Emanuel eVillafan Emanuel eVillafan Cristina eVieira Céline eCosseau Céline eCosseau Christoph eGrunau Christoph eGrunau |
| author_sort | David eRoquis |
| collection | DOAJ |
| description | Schistosoma mansoni is a parasitic plathyhelminth responsible for intestinal schistosomiasis (or bilharziasis), a disease affecting 67 million people worldwide and causing an important economic burden. The schistosomicides hycanthone, and its later proxy oxamniquine, were widely used for treatments in endemic areas during the 20th century. Recently, the mechanism of action, as well as the genetic origin of a stably and Mendelian inherited resistance for both drugs was elucidated in two strains. However, several observations suggested early on that alternative mechanisms might exist, by which resistance could be induced for these two drugs in sensitive lines of schistosomes. This induced resistance appeared rapidly, within the first generation, but was metastable (not stably inherited). Epigenetic inheritance could explain such a phenomenon and we therefore re-analyzed the historical data with our current knowledge of epigenetics. In addition, we performed new experiments such as ChIP-seq on hycanthone treated worms. We found distinct chromatin structure changes between sensitive worms and induced resistant worms from the same strain. No specific pathway was discovered, but genes in which chromatin structure modification were observed are mostly associated with transport and catabolism, which makes sense in the context of the elimination of the drug. Specific differences were observed in the repetitive compartment of the genome. We finally describe what types of experiments are needed to understand the complexity of heritability that can be based on genetic and/or epigenetic mechanisms for drug resistance in schistosomes. |
| first_indexed | 2024-04-14T06:23:54Z |
| format | Article |
| id | doaj.art-02d7b949d7614e528ea7cd12e59af3d3 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T06:23:54Z |
| publishDate | 2014-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-02d7b949d7614e528ea7cd12e59af3d32022-12-22T02:07:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212014-07-01510.3389/fgene.2014.0020797292Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoniDavid eRoquis0David eRoquis1Julie MJ Lepesant2Julie MJ Lepesant3Emanuel eVillafan4Emanuel eVillafan5Cristina eVieira6Céline eCosseau7Céline eCosseau8Christoph eGrunau9Christoph eGrunau10University of Perpignan Via DomitiaCNRSUniversity of Perpignan Via DomitiaCNRSUniversité Lyon 1Red de Estudios Moleculares AvanzadosUniversité Lyon 1University of Perpignan Via DomitiaCNRSUniversity of Perpignan Via DomitiaCNRSSchistosoma mansoni is a parasitic plathyhelminth responsible for intestinal schistosomiasis (or bilharziasis), a disease affecting 67 million people worldwide and causing an important economic burden. The schistosomicides hycanthone, and its later proxy oxamniquine, were widely used for treatments in endemic areas during the 20th century. Recently, the mechanism of action, as well as the genetic origin of a stably and Mendelian inherited resistance for both drugs was elucidated in two strains. However, several observations suggested early on that alternative mechanisms might exist, by which resistance could be induced for these two drugs in sensitive lines of schistosomes. This induced resistance appeared rapidly, within the first generation, but was metastable (not stably inherited). Epigenetic inheritance could explain such a phenomenon and we therefore re-analyzed the historical data with our current knowledge of epigenetics. In addition, we performed new experiments such as ChIP-seq on hycanthone treated worms. We found distinct chromatin structure changes between sensitive worms and induced resistant worms from the same strain. No specific pathway was discovered, but genes in which chromatin structure modification were observed are mostly associated with transport and catabolism, which makes sense in the context of the elimination of the drug. Specific differences were observed in the repetitive compartment of the genome. We finally describe what types of experiments are needed to understand the complexity of heritability that can be based on genetic and/or epigenetic mechanisms for drug resistance in schistosomes.http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00207/fullHycanthoneOxamniquineSchistosoma mansoniepigeneticsResistanceinduction |
| spellingShingle | David eRoquis David eRoquis Julie MJ Lepesant Julie MJ Lepesant Emanuel eVillafan Emanuel eVillafan Cristina eVieira Céline eCosseau Céline eCosseau Christoph eGrunau Christoph eGrunau Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni Frontiers in Genetics Hycanthone Oxamniquine Schistosoma mansoni epigenetics Resistance induction |
| title | Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni |
| title_full | Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni |
| title_fullStr | Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni |
| title_full_unstemmed | Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni |
| title_short | Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni |
| title_sort | exposure to hycanthone alters chromatin structure around specific gene functions and specific repeats in schistosoma mansoni |
| topic | Hycanthone Oxamniquine Schistosoma mansoni epigenetics Resistance induction |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00207/full |
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