Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel

Abstract

Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants.

Mass Spectrometry and Metabolomics—New Approaches for Helminth Biochemical Studies

“…In addition to tegumental damage, PZQ significantly changed the metabolic profile of both sexes of S. mansoni [49]. These data are supported by a recent work where tegumental damage of schistosomes under PZQ exposure was demonstrated through scanning electronic microscopy and optical microscopy [92]. These findings could be helpful for understanding possible targets and pathways of this antischistosomal drug and demonstrates the versatility and potential use of mass spectrometrybased metabolomics for identification of drug targets.…”

Comparative Proteomics Reveals Characteristic Proteins on Praziquantel-resistance inSchistosoma mansoni

“…In regard to collagen alpha chain, Yang and colleagues (Yang et al, 2012)described that silencing the expression of a type of collagen (type V collagen) significantly affects the spawning and egg hatching of S. japonicum , and it also affects the morphology of the worms (Yang et al, 2012). Therefore, it would be very interesting evaluate the role of each of these proteins in PZQ-resistance, specially, collagen alpha chain, since it seems to occur morphological alterations in eggs and worms of S. mansoni PZQ-resistant strain (Pinto-Almeida et al, 2016). Moreover, females of this species, the only gender in which those proteins were found in this work, are more tolerant to PZQ treatment than males (Pinto-Almeida et al, 2015).…”

“…All those results together represent an important finding for the study of PZQ-resistance/susceptibility in S. mansoni , since they allow comparing directly the proteome under both conditions. We believe that the most promising candidates are proteins that appeared associated only to one of the strains, especially those with functions possibly related with the phenotypic alterations observed in (Pinto-Almeida et al, 2016), or previously associated with resistance by others parasites to different drugs. These candidates require special attention in more studies, assessing for instance the level of protection induced by these proteins in animal models infected by both S. mansoni strains, as they may have some involvement on PZQ-resistance phenomenon.…”

Molluscicidal and cercaricidal activities of curcumin on Biomphalaria glabrata and Schistosoma mansoni cercariae

“…However, juvenile parasites, between 7 and 28 days old, appear to be less susceptible to this drug . In addition, studies have shown the emergence of Schistosoma strains that are less sensitive to PZQ …”

“…13 In addition, studies have shown the emergence of Schistosoma strains that are less sensitive to PZQ. [14][15][16][17][18][19] Considering the importance of natural products in drug discovery processes, 20 a wide variety of extracts and compounds isolated from plants have been chemically and biologically investigated against Schistosoma parasites and their invertebrate host, 21,22 as well as other snails. 23 Curcuma longa L. Zingibiraceae, also known as turmeric, is widely used in culinary and folk medicine to treat several diseases.…”