Zülch, F., Holle, M., Hofmann, A. (2024) PLoS ONE 19, e0304791

The use of blockchain technology to establish food traceability chains has the potential to provide transparent information of food stuffs along the entire supply chain and also aid in the documentation or even execution of official food control processes. Particularly in instances where analytical methodologies cannot provide definitive data for food control questions under study, the certificate-based approach of a traceability chain may offer a way of regulatory control for state authorities. Given the rising importance of organic produce and the high share of eggs among the organic produce in the European Union as well as the new EU regulation on organic products and labelling that came into force in 2022, we analyze here how the control of egg production type and marketing standards can be represented within a blockchain-based traceability chain such as to maximize the traceability in compliance with the current relevant EU regulations. Intended for the use by the official food control authorities, a traceability chain for organically produced eggs in the EU would need to be implemented as a permissioned blockchain, since only select entities are allowed to participate. By combining a proof of authority consensus mechanism with issuance of soulbound tokens, we effectively suggest a ‘proof of soulbound authority’ consensus process. The soulbound tokens are issued throughout the administrative chain from the European Commission down to the official food control authorities in individual member states that ultimately certify the control bodies for organic produce. Despite the general limitation of not providing unambiguous proof of the organic status of individual products, the concept discussed here offers advantages with respect to allocation of authority at EU level and therefore might have positive effects beyond the traceability chain.

Rooney, J., Rivera-de-Torre, E., Li, R., Mclean, K., Price, D.R.G., Nisbet, A.J., Laustsen, A.H., Jenkins, T.P., Hofmann, A., Bakshi, S., Zarkan, A., Cantacessi, C. (2024) Comput. Struct. Biotechnol. J. 23, 1522-1533

The complex relationships between gastrointestinal (GI) nematodes and the host gut microbiota have been implicated in key aspects of helminth disease and infection outcomes. Nevertheless, the direct and indirect mechanisms governing these interactions are, thus far, largely unknown. Here, we demonstrate that the excretory-secretory products (ESPs) and extracellular vesicles (EVs) of key GI nematodes contain peptides that, when recombinantly expressed, exert antimicrobial activity in vitro against Bacillus subtilis. In particular, using time-lapse microfluidics microscopy, we demonstrate that exposure of B. subtilis to a recombinant saposin-domain containing peptide from the ‘brown stomach worm’, Teladorsagia circumcincta, and a metridin-like ShK toxin from the ‘barber’s pole worm’, Haemonchus contortus, results in substantial membrane damage, membrane blebbing, and cell lysis. This study provides key evidence of the occurrence of direct mechanisms of worm-microbiota interactions and paves the way for future investigations aimed at deciphering the impact of parasite-associated changes in host gut microbiota composition and function on the pathophysiology of GI helminth infection.

Shanley, H.T., Taki, A.C., Nguyen, N., Wang, T., Byrne, J.J., Ang, C.-S., Leeming, M.G., Nie, S., Williamson, N., Zheng, Y., Young, N.D., Korhonen, P.K., Hofmann, A., Chang, B.C.H., Wells, T.N.C., Häberli, C., Keiser, J., Jabbar, A., Sleebs, B.E., Gasser, R.B. (2024) Int. J. Parasitol. Drugs Drug Resist. 24, 100522

Within the context of our anthelmintic discovery program, we recently identified and evaluated a quinoline derivative, called ABX464 or obefazimod, as a nematocidal candidate; synthesised a series of analogues which were assessed for activity against the free-living nematode Caenorhabditis elegans; and predicted compound-target relationships by thermal proteome profiling (TPP) and in silico docking. Here, we logically extended this work and critically evaluated the anthelmintic activity of ABX464 analogues on Haemonchus contortus (barber’s pole worm) – a highly pathogenic nematode of ruminant livestock. First, we tested a series of 44 analogues on H. contortus (larvae and adults) to investigate the nematocidal pharmacophore of ABX464, and identified one compound with greater potency than the parent compound and showed moderate activity against a select number of other parasitic nematodes (including Ancylostoma, Heligmosomoides and Strongyloides species). Using TPP and in silico modelling studies, we predicted protein HCON_00074590 (a predicted aldo-keto reductase) as a target candidate for ABX464 in H. contortus. Future work aims to optimise this compound as a nematocidal candidate and investigate its pharmacokinetic properties. Overall, this study presents the first steps toward the development of a new anthelmintic with a novel, distinct mechanism of action.