Biology subjects

Dalton, J. P.

Publications and source records attributed to Dalton, J. P..

6 recordsLinked to original sources

bioRxiv2026

Healing helminths: The disease-modifying potential of helminth-derived proteins in animal models of inflammatory disease

Helminths are parasitic worms that secrete a variety of immune-regulating molecules to modulate the hosts inflammatory responses, enabling them to persist within the host over a long period of time, even decades. Their capacity to control host responses has prompted research into helminth-derived molecules as potential therapies for controlling excessive immune and inflammatory activity across a range of diseases. This systematic review with cross-study quantitative analysis aims to synthesize the published data on helminth-derived immunomodulatory peptides/polypeptides/proteins (HDIPs) with a focus on determining the extent of their disease-modifying and anti-inflammatory potential in in vivo animal models of inflammatory disease. In accordance with PRISMA 2020 guidelines, a predefined systematic search of the PubMed, Web of Science and Medline databases identified relevant studies published up to February 2026, and 65 articles were included after screening. We found that, although the HDIPs were assessed in multiple different disease models, most published studies assessed their potential in mouse models of colitis, asthma, arthritis and sepsis. Twenty species from which >65 isolated HDIPs were derived were tested in these models, with the trematode, Fasciola hepatica, and the nematode, Acanthocheilonema viteae, the most explored species. A common property of the HDIPs was the ability to significantly reduce disease severity across the in vivo animal models of inflammatory disease, underpinned by a decrease in pro-inflammatory cytokine levels and an increase in anti-inflammatory cytokine levels. Overall, this systematic review with cross-study quantitative analysis not only synthesizes the existing literature in this field but also highlights the disease-modifying and anti-inflammatory potential of HDIPs for a range of diseases in which immunoregulatory therapeutics may improve disease outcomes. It also encourages accelerated advancement of these helminth-derived molecules into first-in-human clinical trials.

immunology↗

bioRxiv2025

The anti-inflammatory potential of helminth-derived peptides/polypeptides: A systematic review in cellular models of inflammation

Helminths are parasitic worms that secrete a plethora of immune regulatory molecules which allow them to dampen inflammatory responses by their hosts immune system to ensure their survival within the host. Their ability to have a compatible existence with their host has led to research into the potential therapeutic effects of helminth-derived molecules for suppression of overactive immune and inflammatory responses in a wide variety of diseases. This systematic review aims to synthesize the published data on helminth-derived peptides/polypeptides (HDPs) with a focus on determining the extent to which they modulate the inflammatory response in in vitro cellular models of inflammation. In accordance with PRISMA 2020 guidelines, a predefined systematic search of the PubMed, Web of Science and Medline databases identified relevant studies published up to August 2025, and 79 articles were included after screening. We found that most published studies used LPS or Concanavalin A stimulated macrophages, peripheral blood mononuclear cells or dendritic cells as the cellular model of inflammation. Twenty helminth species from which >60 isolated HDPs were derived were tested in these models, with the nematodes, Haemonchus contortus and Acanthocheilonema viteae, and the trematode, Fasciola hepatica, the most explored species. A common property of these molecules was to ability to significantly reduce the expression or production of pro-inflammatory cytokines such as IL-12, IL-1{beta}, IL-6 and TNF, and significantly increase the expression or production of anti-inflammatory cytokines such as IL-10, TGF{beta} and IL-4. The effects on other cytokines, including IFN{gamma} which is known to have both pro- and anti-inflammatory effects, were less consistent, with HDPs either decreasing or increasing the levels of this cytokine. This systematic review synthesizes the existing literature in this field and shows that the HDPs secreted by several helminth species have consistently demonstrated effects though modification of cytokine levels and, as such, have therapeutic potential in conditions in which overactive immune and inflammatory responses play a pathogenic role.

immunology↗

bioRxiv2024

Moonlighting on the Fasciola hepatica tegument: enolase, a glycolytic enzyme, interacts with the extracellular matrix and fibrinolytic system of the host

Enolase is a 47 kDa enzyme that functions within the glycolysis and gluconeogenesis pathways involved in the reversible conversion of D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP). However, in the context of host-pathogen interactions, enolase from different species of parasites, fungi and bacteria have been shown to contribute to adhesion processes by binding to proteins of the host extracellular matrix (ECM), such as fibronectin (FN) or laminin (LM). In addition, enolase is a plasminogen (PLG)-binding protein and induces its activation to plasmin, the main protease of the host fibrinolytic system. These secondary moonlighting functions of enolase are suggested to facilitate pathogen migration through host tissues. This study aims to uncover the moonlighting role of enolase from the parasite Fasciola hepatica, shedding light on its relevance to host-parasite interactions in fasciolosis, a global zoonotic disease of increasing concern. A purified recombinant form of F. hepatica enolase (rFhENO), functioning as an active homodimeric glycolytic enzyme of [~]94 kDa, was successfully obtained, fulfilling its canonical role. Immunoblotting studies on adult worm extracts showed that the enzyme is present in the tegument and the excretory/secretory products of the parasite, which supports its key role at the host-parasite interface. Confocal immunolocalisation studies of the protein in newly excysted juveniles and adult worms also localised its expression within the parasite tegument. Finally, we showed by ELISA that rFhENO can act as a parasitic adhesin by binding host LM, but not FN. rFhENO also binds PLG and enhances its conversion to plasmin in the presence of the tissue-type and urokinase-type PLG activators (t-PA and u-PA). This moonlighting adhesion-like function of the glycolytic protein enolase could contribute to the mechanisms by which F. hepatica efficiently invades and migrates within its host and encourages further research efforts that are designed to impediment this function by vaccination or drug design. AUTHOR SUMMARYFasciola hepatica is a parasitic worm causing fasciolosis, primarily affecting herbivorous mammals and posing a significant veterinary problem. Furthermore, it is a zoonosis, meaning it can be transmitted to humans. F. hepatica enters the definitive host through ingestion of contaminated aquatic plants, migrating through the intestine to settle in the liver bile ducts, where it matures into the adult stage. To migrate, it utilizes various invasion strategies, including the use of multifunctional proteins, known as moonlighting. In this study, we produced and molecularly characterized the parasitic enzyme enolase as a moonlighting protein to understand F. hepatica invasion mechanisms. We produced recombinant enolase with glycolytic activity, its canonical function in parasite energy production. Additionally, we localised this enzyme in the parasites tegument, in direct contact with the host, and demonstrated its ability to elicit an immune response early in ovine infection. Finally, we demonstrated the ability of enolase to interact with the extracellular matrix and the hosts fibrinolysis, a proteolytic system responsible for dissolving blood clots. These secondary functions of F. hepatica enolase, described here for the first time, along with its localisation and immunogenicity, suggest this protein as an interesting antigen for fasciolosis diagnosis and/or control.

molecular biology↗

bioRxiv2022

Production of a functionally active recombinant SARS-CoV-2 (COVID-19) 3C-Like protease and a soluble inactive 3C-like protease-RBD chimeric in a prokaryotic expression system

During the SARS-CoV-2 intracellular life-cycle, two large polyproteins, pp1a and pp1ab, are produced. Processing of these by viral cysteine proteases, the papain-like protease (PLpro) and the chymotrypsin-like 3C-like protease (3CL-pro) release non-structural proteins necessary for the establishment of the viral replication and transcription complex (RTC), crucial for viral replication. Hence, these proteases are considered prime targets against which anti-COVID-19 drugs could be developed. Here, we describe the expression of a highly soluble and functionally active recombinant 3CL-pro using Escherichia coli BL21 cells. In addition, we assessed the ability of our 3CL-pro to function as a carrier for the Receptor Binding Domain (RBD) of the Spike protein. The co-expressed chimeric protein, 3CLpro-RBD, did not exhibit 3CL-pro activity, but its enhanced solubility made purification easier and improved RBD antigenicity when tested against serum from vaccinated individuals in ELISAs. When used to immunise mice, the 3CLpro-RBD chimer elicited antibodies mainly to the 3CL-pro portion of the molecule indicating that a different chimeric composition (i.e., RBD/full Spike-3CLpro) or expression system (i.e., mammalian cells), might be required to produce and deliver a RBD with immunogenicity similar to the native protein. Chimeric proteins containing the 3CL-pro could represent an innovative approach to developing new COVID-19 vaccines.

biochemistry↗

bioRxiv2016

A novel restraint device for injection of Galleria mellonella larvae that minimises the risk of accidental operator needle stick injury

Larvae of the insect Galleria mellonella are increasingly being used for studying pathogenic microbes and their virulence mechanisms, and as a rapid model for screening novel antimicrobial agents. The larvae (waxworms) are most frequently infected by injection of pathogenic organisms into the haemocoel through the insects prolegs. The mostly widely used method for restraining the waxworms for injection is by grasping them between the operators fingers, which puts the operator at risk of needle stick injury, an important consideration when working with highly pathogenic and/or drug-resistant microorganisms. While use of a stab proof glove can reduce this risk of injury, it does so at the loss of manual dexterity and speed, resulting in a more labour-intensive and cumbersome assay. We describe a simple cost effective device (the so-called Galleria Grabber) for restraining waxworms for injection that keeps the operators fingers clear of the needle thus reducing the risk of injury.

microbiology↗

bioRxiv2016

Effect of common and experimental anti-tuberculosis treatments on Mycobacterium tuberculosis growing as biofilms

Much is known regarding the antibiotic susceptibility of planktonic cultures of Mycobacterium tuberculosis, the bacterium responsible for the lung disease tuberculosis (TB). As planktonically-grown M. tuberculosis are unlikely to be entirely representative of the bacterium during infection, we set out to determine how effective a range of anti-mycobacterial treatments were against M. tuberculosis growing as a biofilm, a bacterial phenotype known to be more resistant to antibiotic treatment. Light levels from bioluminescently-labelled M. tuberculosis H37Rv (strain BSG001) were used as a surrogate for bacterial viability, and were monitored before and after 1 week of treatment. After treatment, biofilms were disrupted, washed and inoculated into fresh broth and plated onto solid media to rescue any surviving bacteria. We found that in this phenotypic state M. tuberculosis was resistant to the majority of the compounds tested. Minimum inhibitory concentrations (MICs) increased by 20-fold to greater than 1000-fold, underlying the potential of this phenotype to cause significant problems during treatment.

microbiology↗