Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Abstract

Antimicrobial Peptides (AMPs) are immune effectors that are key components of the invertebrate innate immune system providing protection against pathogenic microbes. Parasitic helminths (phylum Nematoda and phylum Platyhelminthes) share complex interactions with their hosts and closely associated microbiota that are likely regulated by a diverse portfolio of antimicrobial immune effectors including AMPs. Knowledge of helminth AMPs has largely been derived from nematodes, whereas the flatworm AMP repertoire has not been described. This study highlights limitations in the homology-based approaches, used to identify putative nematode AMPs, for the characterisation of flatworm AMPs, and reveals that innovative algorithmic AMP prediction approaches provide an alternative strategy for novel helminth AMP discovery. The data presented here: (i) reveal that flatworms do not encode traditional lophotrochozoan AMP groups (Big Defensin, CSαβ peptides and Myticalin); (ii) describe a unique integrated computational pipeline for the discovery of novel helminth AMPs; (iii) reveal >16,000 putative AMP-like peptides across 127 helminth species; (iv) highlight that cysteine-rich peptides dominate helminth AMP-like peptide profiles; (v) uncover eight novel helminth AMP-like peptides with diverse antibacterial activities, and (vi) demonstrate the detection of AMP-like peptides from Ascaris suum biofluid. These data represent a significant advance in our understanding of the putative helminth AMP repertoire and underscore a potential untapped source of antimicrobial diversity which may provide opportunities for the discovery of novel antimicrobials. Further, unravelling the role of endogenous worm-derived antimicrobials and their potential to influence host-worm-microbiome interactions may be exploited for the development of unique helminth control approaches.

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

“…A recent analysis of publicly available sequence data from a range of parasitic helminths identified over 16,000 putative AMPs encoded by the genomes of 127 worm species [75] . Building upon our findings and those by Irvine et al .…”

“…Building upon our findings and those by Irvine et al . [75] , in depth structural and functional characterisations of helminth-derived AMPs may provide clarity on mechanisms of worm-microbiota interactions in vivo, and thus pave the way toward the development of novel and sustainable approaches to control parasitic diseases amid the ever-increasing threat of anthelmintic resistance. For instance, the rational manipulation of the ruminant gut microbiota (e.g.…”

Advancing Strongyloides omics data: bridging the gap with Caenorhabditis elegans

“…Integrating in silico genomics and transcriptomics with LC-MS/MS has further advanced proteomic and peptidomics research [159], and these approaches are beginning to emerge within parasitic nematode literature [160].…”

“…Since the advent of high-throughput peptidomics only H. contortus has been studied in addition to A. suum , and the focus has primarily been the identification of neuropeptide and antimicrobial peptide profiles in somatic extracts [150,151,158]. Integrating in silico genomics and transcriptomics with LC–MS/MS has further advanced proteomic and peptidomics research [159], and these approaches are beginning to emerge within parasitic nematode literature [160].…”