Microplastics and seafood: lower trophic organisms at highest risk of contamination

Microplastic debris is a prevalent global pollutant that poses a risk to marine organisms and ecological processes. It is also suspected to pose a risk to marine food security; however, these risks are currently poorly understood. In this review, we seek to understand the current knowledge pertaining to the contamination of commercially important fished and farmed marine organisms with microplastics, with the aim of answering the question “Does microplastic pollution pose a risk to marine food security?“. A semi-systematic review of studies investigating the number of microplastics found in commercially important organisms of different trophic levels suggests that microplastics do not biomagnify, and that organisms at lower trophic levels are more likely to contaminated by microplastic pollution than apex predators. We address the factors that influence microplastic consumption and retention by organisms. This research has implications for food safety and highlights the risks of microplastics to fisheries and aquaculture, and identifies current knowledge gaps within this research field

Demonstration of the anthelmintic potency of marimastat in the Heligmosomoides polygyrus rodent model

In the course of a structure based drug discovery program the known anticancer candidate marimastat was uncovered as a potent inhibitor of an enzyme in nematode cuticle biogenesis. It was shown to kill Caenorhabditis elegans, and the sheep parasites Haemonchus contortus and Teladorsagia circumcinta via an entirely novel nematode-specific pathway, specifically by inhibiting cuticle-remodelling enzymes that the parasites require for the developmentally essential moulting process. This discovery prompted an investigation of the compound's effect on Heligmosomoides polygyrus parasites in a mouse model of helminth infection. Mice were administered the drug via oral gavage daily from day of infection for a period of 2 wk. A second group received the drug via intra-peritoneal implantation of an osmotic minipump for 4 wk. Control groups were administered identical volumes of water by oral gavage in both cases. Counts of H. polygyrus faecal egg and larval load showed that marimastat effected a consistent and significant reduction in egg laying, and a consistent but minor reduction in adult worm load when administered every day, starting on the first day of infection. However, the drug failed to have any significant effect on egg counts or worm burdens when administered to mice with established infections. Therefore, marimastat does not appear to show promise as an anthelmintic in gastrointestinal nematode infections, although other metalloproteases such as batimastat may prove more effective

Impact of polyester and cotton microfibers on growth and sublethal biomarkers in juvenile mussels

Anthropogenic microfibres are a prevalent, persistent and globally distributed form of marine debris. Evidence of microfibre ingestion has been demonstrated in a range of organisms, including Mytilus spp. (mussels), but the extent of any impacts on these organisms are poorly understood. This study investigates, for the first time, the effect of exposing juvenile mussels to polyester and cotton microfibres at environmentally relevant concentrations (both current and predicted future scenarios) over a chronic timescale (94 days). Sublethal biomarkers included growth rate, respiration rate and clearance rate. Mussels were exposed to polyester (median length 149 µm) and cotton (median length 132 µm) microfibres in three treatments: polyester (~ 8 fibres L−1), polyester (~ 80 fibres L−1) and cotton (~ 80 fibres L−1). Mussels exposed to 80 polyester or cotton microfibres L−1 exhibited a decrease in growth rate of 35.6% (polyester) and 18.7% (cotton), with mussels exposed to ~ 80 polyester microfibres L−1 having a significantly lower growth rate than the control population (P < 0.05). This study demonstrates that polyester microfibres have the potential to adversely impact upon mussel growth rates in realistic future scenarios, which may have compounding effects throughout the marine ecosystem and implications for commercial viability

Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice

The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases

Does microplastic pollution pose a risk to marine life and food security?

Microplastics are a persistent and pervasive pollutant, ubiquitous in marine environments worldwide. Owing to their size and prevalence, microplastics have been demonstrated to be ingested by marine organisms throughout the food chain. However, the risks that microplastics pose to commercially exploited marine organisms are poorly elucidated. There is a lack of information pertaining to the inputs of microplastic into farmed marine species, the effect of environmentally relevant concentrations of microplastics on commercially important marine organisms, and ultimately whether microplastics may pose a risk to food security. In this thesis, I combine literature analysis with novel quantitative data through a suite of microplastic identification techniques and exposure experiments to explore these gaps in our current knowledge. My data demonstrates that while commercially-important organisms throughout the food chain ingest microplastics, lower trophic level organisms contain the highest body burdens of microplastics and there is little evidence that microplastics biomagnify. I identify that prolonged exposure to environmentally realistic concentrations of microplastic fibres results in lower growth rates in the commercially-exploited marine bivalve Mytilus edulis. I highlight a novel pathway for the contamination of farmed fish with microplastics via contaminated aquaculture feed. Finally, I performed a methods comparison of commonly used microplastic identification techniques to reveal micro-FTIR and py-GCMS are the most effective means for characterizing microplastics in complex samples, but resultant data are not readily comparable. My thesis draws attention to the prevalence of semi-synthetic and cotton microfibres in marine samples, and how their environmental risk is often ignored. This research contributes to our knowledge of how microplastics and other anthropogenic particles can contaminate aquaculture feed and adversely affect lower trophic level organisms, posing a risk to marine food security, and guides researchers as to the best techniques to use when analysing complex organic samples

Demonstration of the Anthelmintic Potency of Marimastat in the Heligmosomoides Polygyrus Rodent Model

In the course of a structure based drug discovery program the known anticancer candidate marimastat was uncovered as a potent inhibitor of an enzyme in nematode cuticle biogenesis. It was shown to kill Caenorhabditis elegans, and the sheep parasites Haemonchus contortus and Teladorsagia circumcinta via an entirely novel nematode-specific pathway, specifically by inhibiting cuticle-remodelling enzymes that the parasites require for the developmentally essential moulting process. This discovery prompted an investigation of the compound's effect on Heligmosomoides polygyrus parasites in a mouse model of helminth infection. Mice were administered the drug via oral gavage daily from day of infection for a period of 2 wk. A second group received the drug via intra-peritoneal implantation of an osmotic minipump for 4 wk. Control groups were administered identical volumes of water by oral gavage in both cases. Counts of H. polygyrus faecal egg and larval load showed that marimastat effected a consistent and significant reduction in egg laying, and a consistent but minor reduction in adult worm load when administered every day, starting on the first day of infection. However, the drug failed to have any significant effect on egg counts or worm burdens when administered to mice with established infections. Therefore, marimastat does not appear to show promise as an anthelmintic in gastrointestinal nematode infections, although other metalloproteases such as batimastat may prove more effective