FN Archimer Export Format
PT J
TI The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities
BT 
AF GEYER, Kathrin K.
   MUNSHI, Sabrina E.
   VICKERS, Martin
   SQUANCE, Michael
   WILKINSON, Toby J.
   BERRAR, Daniel
   CHAPARRO, Cristian
   SWAIN, Martin T.
   HOFFMANN, Karl F.
AS 1:1;2:1;3:2;4:1;5:3;6:4;7:5;8:1;9:1;
FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;
C1 Aberystwyth Univ, IBERS, Edward Llwyd Bldg, Aberystwyth SY23 3DA, Dyfed, Wales.
   John Innes Ctr, Dept Cell & Dev Biol, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England.
   Univ Edinburgh, Roslin Inst, Easter Bush Campus, Roslin EH25 9RG, Midlothian, Scotland.
   Tokyo Inst Technol, Data Sci Lab, Tokyo 1528550, Japan.
   Univ Perpignan Via Domitia, 58 Ave Paul Alduy,Bat R, F-66860 Perpignan, France.
C2 UNIV ABERYSTWYTH, UK
   JOHN INNES CTR, UK
   UNIV EDINBURGH, UK
   TOKYO INST TECHNOL, JAPAN
   UNIV PERPIGNAN, FRANCE
UM IHPE
IN DOAJ
IF 2.951
TC 15
UR https://archimer.ifremer.fr/doc/00615/72703/71747.pdf
   https://archimer.ifremer.fr/doc/00615/72703/71748.xml
   https://archimer.ifremer.fr/doc/00615/72703/71749.xlsx
   https://archimer.ifremer.fr/doc/00615/72703/71750.xlsx
   https://archimer.ifremer.fr/doc/00615/72703/71751.xlsx
   https://archimer.ifremer.fr/doc/00615/72703/71752.xlsx
   https://archimer.ifremer.fr/doc/00615/72703/71753.xlsx
   https://archimer.ifremer.fr/doc/00615/72703/71754.xlsx
   https://archimer.ifremer.fr/doc/00615/72703/71755.pdf
   https://archimer.ifremer.fr/doc/00615/72703/71756.pdf
LA English
DT Article
DE ;Schistosoma mansoni;Epigenetics;5-Azacytidine;Fecundity;RNA-Seq;Protein synthesis;Stem cells
AB Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development. While these anti-fecundity effects were associated with a loss of DNA methylation, other molecular processes affected by 5-AzaC were not examined at the time. By comparing the transcriptomes of 5-AzaC-treated females to controls, we provide evidence that this ribonucleoside analogue also modulates other crucial aspects of schistosome egg-laying biology. For example, S. mansoni gene products associated with amino acid-, carbohydrate-, fatty acid-, nucleotide-and tricarboxylic acid (TCA)-homeostasis are all dysregulated in 5-AzaC treated females. To validate the metabolic pathway most significantly affected by 5-AzaC, amino acid metabolism, nascent protein synthesis was subsequently quantified in adult schistosomes. Here, 5-AzaC inhibited this process by 68% +/- 16.7% (SEM) in maleand 81% +/- 4.8% (SEM) in female-schistosomes. Furthermore, the transcriptome data indicated that adult female stem cells were also affected by 5-AzaC. For instance, 40% of transcripts associated with proliferating schistosome cells were significantly down-regulated by 5-AzaC. This finding correlated with a considerable reduction (95%) in the number of 5-ethynyl-2'-deoxyuridine (EdU) positive cells found in 5-AzaC-treated females. In addition to protein coding genes, the effect that 5-AzaC had on repetitive element expression was also assessed. Here, 46 repeats were found differentially transcribed between 5-AzaC-treated and control females with long terminal repeat (LTR) and DNA transposon classes being amongst the most significant. This study demonstrates that the anti-fecundity activity of 5-AzaC affects more than just DNA methylation in schistosome parasites. Further characterisation of these processes may reveal novel targets for schistosomiasis control.
PY 2018
PD AUG
SO International Journal For Parasitology-drugs And Drug Resistance
SN 2211-3207
PU Elsevier Sci Ltd
VL 8
IS 2
UT 000438125200007
BP 213
EP 222
DI 10.1016/j.ijpddr.2018.03.006
ID 72703
ER

EF