RT Journal Article SR Electronic T1 Comparative Proteomics Reveals Characteristic Proteins on Praziquantel-resistance in Schistosoma mansoni JF bioRxiv FD Cold Spring Harbor Laboratory SP 314724 DO 10.1101/314724 A1 António Pinto-Almeida A1 Tiago Mendes A1 Pedro Ferreira A1 Silvana Belo A1 Fernanda de Freitas Anibal A1 Silmara Marques Allegretti A1 Emanuel Carrilho A1 Ana Afonso YR 2018 UL http://biorxiv.org/content/early/2018/05/09/314724.abstract AB The extensive use of Praziquantel (PZQ), the only drug available to treat schistosomiasis, has brought concern about the emergence of PZQ-resistance/tolerance by Schistosoma spp., thus reaffirming an urge for the development of new treatment alternatives. Therefore, it is imperative and urgent to study this phenomenon trying to understand what is involved in its occurrence. Studies of Schistosoma spp. genome, transcriptome and proteome are crucial to better understand this situation. By stepwise drug pressure from a fully susceptible parasite strain, our group selected a S. mansoni variant strain stably resistant to PZQ and isogenic to its fully susceptible parental counterpart, except for the genetic determinants of PZQ-resistance phenotype. Based on this, the objective of this study was to compare the proteomes of both strains, identifying proteins from male and female adult worms of PZQ-resistant and PZQ-susceptible strains, exposed and not exposed to PZQ, which were separated by high-resolution two-dimensional electrophoresis and sequenced by high throughput LC-MS/MS. Likewise, this work is extremely relevant since for the first time the proteome of a S. mansoni PZQ-resistant strain is studied and compared to the proteome of the respective S. mansoni PZQ-susceptible strain. This study identified 60 S. mansoni proteins, some of which differentially expressed in either strain, which may putatively be involved in the PZQ-resistance phenomenon. This information represents substantial progress towards deciphering the worm proteome. Furthermore, these data may constitute an informative source for further investigations into PZQ-resistance and increase the possibility of identifying proteins related to this condition, possibly contributing to avoid or decrease the likelihood of development and spread of PZQ-resistance. This is an innovative study that opens doors to PZQ-resistance surveys, contributing to discover a solution to PZQ-resistance problem, as suggests new potential targets for study.2-DEtwo-dimensional electrophoresisACNacetonitrileBHBelo HorizonteDHPCdiheptanoyl-snglycero-3-phosphatidylcholineDTTdithiothreitolEPZQexposed to PraziquantelFAformic acidGOgene ontologyIAAiodoacetamideIEFisoelectric focusingIHMT/UNLInstituto de Higiene e Medicina Tropical, Universidade Nova de LisboaIMPDHInosine-5’-monophosphate dehydrogenaseIPGimmobilized pH gradientLC-MS/MSliquid chromatography–tandem mass spectrometryMSmass spectrometryNEPZQnot exposed to PraziquantelPKCprotein kinase CPZQPraziquantelRFresistant femaleRMresistant maleRSresistant strainSDS-PAGEsodium dodecyl sulfate – polyacrylamide gel electrophoresisSFsusceptible femaleSMsusceptible maleSSsusceptible strainTFAtrifluoracetic acid