We have successfully employed a new bioprospecting-based approach to discover new cationic antimicrobial peptides (CAMPs) from the American alligator (Alligator mississippiensis) and Komodo dragon (Varanus komodoensis). Due to the alarming increase in antibiotic resistance, there is growing interest in CAMPs and their development into antibacterial therapeutics. CAMPs are a structurally- and sequence-diverse family of peptides produced by all organisms, forming the foundation of innate immunity in higher species. They represent a pre-screened library of antimicrobial biomolecules that evolved to defend hosts from invading pathogens. Despite their promise as potentially important weapons in our fight against emerging MDR bacteria, the discovery of new CAMPs has been challenging using conventional proteomic strategies. To address this challenge, we have developed a bioprospecting-based approach to CAMP discovery that seamlessly integrates peptide identification and assessment. This process brings together hydrogel particle-based peptide harvesting, high resolution-high accuracy tandem mass spectrometry (MS/MS), and large-scale de novo sequencing in order to preferentially enrich, detect, and identify CAMPs from complex biological samples. CAMP candidates are evaluated for their antimicrobial and anti-biofilm effects. Because this approach captures the sequences of intact, native peptides, it detects and identifies both traditional classes of CAMPs and those peptides that are inaccessible using conventional methods, including alternative CAMP isoforms, new peptides, and fragments of larger proteins. Our analyses of American alligator and Komodo dragon plasma led to the discovery of multiple new CAMPs, including peptides that are effective against multidrug resistant bacteria and biothreat agents.

Bioprospecting and the discovery of cationic antimicrobial peptides from American alligator (Alligator mississippiensis) and Komodo dragon (Varanus komodoensis)

254th National Meeting (2017)

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