Identification and Characterisation of Nematode-derived Antimicrobial Peptides to Tackle Emerging Antimicrobial Resistance


A Irvine1; S Huws1; L Atkinson1; A Mousley1
1 Queen's University Belfast, UK


The emergence of antimicrobial resistance (AMR) is a serious threat to the control of disease in human and animals worldwide. As traditional antibiotics fail, the discovery of novel antimicrobials is key to replacing those that have, or soon will, become ineffective. Antimicrobial peptides (AMPs) are natural antimicrobials produced as part of the innate immune response and are appealing contenders in the quest for novel antimicrobials; indeed, a number of AMPs are already in clinical trials underpinning their potential. Invertebrates lack an adaptive immune response and therefore rely on AMPs to combat microbial threats. This is of particular importance to parasitic nematodes which often live in microbial-rich environments, such as the gastrointestinal system of their host. Profiling the AMP armoury of parasitic nematodes may uncover AMPs with therapeutic potential as novel antimicrobials to tackle AMR. In addition, the role of endogenous AMPs in parasites as the first line of defense against invading pathogens may provide opportunities for the identification of novel anti-worm therapies.

In this study we adopted an in-silico approach to the identification and classification of AMPs across phylum Nematoda. Bioinformatics and computational AMP prediction tools were employed to identify >2000 putative AMPs from 96 nematode species. Putative nematode AMPs were categorised into four known AMP families (Defensins, Cecropins, Nemapores and Glycine Rich Secreted Peptides) based on family-specific sequence similarity and motif identity. The Glycine Rich Secreted Peptides (GRSPs) were the most prevalent amongst the Nematoda, followed by the defensins and nemapores. The cecropins were restricted to the order Ascaridida suggesting that they play an Ascarid-specific role. Clade 8 and Clade 2 species displayed a much reduced AMP profile relative to other nematode clades; this was particularly evident in clade 2 Trichinella and Trichuris species which have both a reduced number and diversity of known AMP families. This may suggest the existence of clade 2 specific AMP families which requires further investigation. The number of putative AMPs in each family varied between species highlighting that the parasite AMP profile is species dependent and is highly adapted to individual lifestyles and lifecycles. Future analysis of nematode AMPs will aim to probe the range of antimicrobial activity displayed by nematode AMPs and investigate the importance of AMPs to nematode biology, exploring tissue-, sex- and life stage- specific AMP expression. 

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