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.