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Discovery of Novel Antimicrobial Peptides from Varanus komodoensis (Komodo Dragon) by Large-Scale Analyses and De-Novo-Assisted Sequencing Using Electron-Transfer Dissociation Mass Spectrometry

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Barney M. Bishop*† , Melanie L. Juba†, Paul S. Russo‡, Megan Devine†, Stephanie M. Barksdale§, Shaylyn Scott†, Robert Settlage∥, Pawel Michalak⊥, Kajal Gupta#, Kent Vliet▽, Joel M. Schnur#, and Monique L. van Hoek§
J. Proteome Res., Article ASAP
Komodo dragons are the largest living lizards and are the apex predators in their environs. They endure numerous strains of pathogenic bacteria in their saliva and recover from wounds inflicted by other dragons, reflecting the inherent robustness of their innate immune defense. We have employed a custom bioprospecting approach combining partial de novo peptide sequencing with transcriptome assembly to identify cationic antimicrobial peptides from Komodo dragon plasma. Through these analyses, we identified 48 novel potential cationic antimicrobial peptides. All but one of the identified peptides were derived from histone proteins. The antimicrobial effectiveness of eight of these peptides was evaluated against Pseudomonas aeruginosa (ATCC 9027) and Staphylococcus aureus (ATCC 25923), with seven peptides exhibiting antimicrobial activity against both microbes and one only showing significant potency against P. aeruginosa. This study demonstrates the power and promise of our bioprospecting approach to cationic antimicrobial peptide discovery, and it reveals the presence of a plethora of novel histone-derived antimicrobial peptides in the plasma of the Komodo dragon. These findings may have broader implications regarding the role that intact histones and histone-derived peptides play in defending the host from infection. Data are available via ProteomeXChange with identifier PXD005043.

—  Department of Chemistry and Biochemistry, George Mason University, 10920 George Mason Circle, 4C7, Manassas, Virginia, 20110, United States ‡ Center for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, 1A9, Manassas, Virginia 20110, United States § School of Systems Biology, George Mason University, 10920 George Mason Circle, 1H8, Manassas, Virginia 20110, United States ∥ Advanced Research Computing, Virginia Polytechnic Institute and State University, 620 Drillfield Drive, Blacksburg, Virginia 24061, United States ⊥ Biocomplexity Institute, Virginia Polytechnic Institute and State University, 1015 Life Science Circle, Blacksburg, Virginia 24061, United States # College of Science, George Mason University, 4400 University Drive, 5C3, Fairfax, Virginia 22030, United States â–½ Department of Biology, University of Florida, 876 Newell Drive, PO Box 118525, Gainesville, Florida 32511, United States

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