Search bioRxiv⌕ Search

Biology subjects

Allegretti, S. M.

Publications and source records attributed to Allegretti, S. M..

2 recordsLinked to original sources

Heterochromatin protein 1 (HP1) of Schistosoma mansoni: non-canonical chromatin landscape and fitness effects

Heterochromatin protein 1 (HP1) is widespread in several organisms playing a role in control of gene expression by heterochromatin formation and maintenance of silent chromatin. Schistosoma mansoni is a human parasite that is responsible for Schistosomiasis, a tropical neglected disease in the tropical and subtropical areas in the world, where the intermediate host Biomphalaria glabrata is present. In this study we attempted to investigate if the SmHP1 is enriched in S. mansoni chromatin in cercariae larvae stage, compared with another larvae stage sporocysts and its importance for S. mansoni life cycle progression and parasite fitness. We used ChIPmentation with commercial antibody ab109028 that passed in-house quality control. Our data show that S. mansoni HP1 enrichment is non-canonical with a peak at the transcription end sites of protein coding genes. We did not find strong differences in SmHP1 chromatin landscapes between sporocysts and cercariae. Knock-down of SmHP1 in schistosomula and in vivo experiments in mice unexpectedly increased parasite fitness. Our results suggest that SmHP1 may influence chromatin structure in a non-canonical way in S. mansoni stages and may play a role in regulation of parasite fitness.

molecular biology↗

Comparative Proteomics Reveals Characteristic Proteins on Praziquantel-resistance in Schistosoma mansoni

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.

pharmacology and toxicology↗