Authors

J Rooney²; E Rivera-de-Torre³; R Li⁴; K Mclean¹; DR Price¹; AJ Nisbet¹; A Hofmann⁶; S Bakshi⁴; A Zarkan⁵; C Cantacessi²;  ¹ Moredun Research Institute, UK;  ² Department of Veterinary Medicine, University of Cambridge, UK;  ³ Department of Biotechnology and Biomedicine, Technical University of Denmark, Denmark;  ⁴ Department of Engineering, University of Cambridge,, UK;  ⁵ Department of Genetics, University of Cambridge, UK;  ⁶ Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Germany

Discussion

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. This presentation will describe the results of our recent experiments demonstrating 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 show 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. Data from our study support the hypothesis that GI nematodes may modulate the composition of the vertebrate gut microbiota directly via the secretion of antimicrobial peptides, and pave the way for future investigations aimed at deciphering the impact of such changes on the pathophysiology of GI helminth infection and disease. However, it is highly likely that worm-microbiota crosstalk occurs through a complex network of direct and indirect mechanisms that act synergistically to enhance parasite survival in a hostile environment. Unravelling the complexities of helminth-host microbiome relationships may lead to a better understanding of helminth biology and to the discovery and development of novel and sustainable parasite control strategies.