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.

Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug. Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. This work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni.

The Estremadura Spur pockmarks are a unique and unexplored ecosystem located in the North Atlantic, off the coast of Portugal. A total of 85 marine-derived actinomycetes were isolated and cultured from sediments collected from this ecosystem at a depth of 200 to 350 m. Nine genera, Streptomyces, Micromonospora, Saccharopolyspora, Actinomadura, Actinopolymorpha, Nocardiopsis, Saccharomonospora, Stackebrandtia, and Verrucosispora were identified by 16S rRNA gene sequencing analyses, from which the first two were the most predominant. Non-targeted LC-MS/MS, in combination with molecular networking, revealed high metabolite diversity, including several known metabolites, such as surugamide, antimycin, etamycin, physostigmine, desferrioxamine, ikarugamycin, piericidine, and rakicidin derivatives, as well as numerous unidentified metabolites. Taxonomy was the strongest parameter influencing the metabolite production, highlighting the different biosynthetic potentials of phylogenetically related actinomycetes; the majority of the chemical classes can be used as chemotaxonomic markers, as the metabolite distribution was mostly genera-specific. The EtOAc extracts of the actinomycete isolates demonstrated antimicrobial and antioxidant activity. Altogether, this study demonstrates that the Estremadura Spur is a source of actinomycetes with potential applications for biotechnology. It highlights the importance of investigating actinomycetes from unique ecosystems, such as pockmarks, as the metabolite production reflects their adaptation to this habitat.

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.

In recent decades, narratives about the sustainable ocean economy and the blue economy have gained prominence. However, these terms remain fluid, reflecting the unprecedented scale and scope of ocean-related economic activities. Despite this ambiguity, the sustainable ocean economy (SOE) has received significant attention for its role in boosting national accounts and supporting development. The relevance of the SOE for Small Island Developing States (SIDS) and least developed countries (LDCs) is evident. Through three case studies – two from SIDS and one from an LDC – we illustrate the current realities of implementing the SOE. This chapter delves further into the challenges and opportunities for SIDS and LDCs in tackling pressing ocean issues. It focuses on the status and progress towards achieving target 14.7 and other related Sustainable Development Goals (SDGs), particularly concerning the sustainable use of marine resources, including fisheries, aquaculture, and tourism, and the resulting economic benefits. This chapter examines the challenges and opportunities these nations face in addressing critical ocean issues and how the SOE contributes to achieving the SDGs.