Structural and functional analyses of nematode-derived antimicrobial peptides support the occurrence of direct mechanisms of worm-microbiota interactions

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. In this proof-of-concept study, 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 cell lysis and significantly reduced growth rates. Data from this 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.