Novel antimicrobial peptides and peptide-microbiome crosstalk in Appalachian salamander skin

Abstract Using multi-omics tools, we discovered new antimicrobial peptides (AMPs) and examined AMP-microbial interactions in three Appalachian salamander species (Plethodon cinereus, Eurycea bislineata and Notophthalmus viridescens). We conducted skin transcriptomics (n = 13) and proteomics (n = 91) to identify 200+ candidate AMPs. With candidate AMPs, we identified correlations with skin microbiomes and synthesized 20 peptides to challenge against pathogens of amphibians (Batrachochytrium dendrobatidis: Bd) and humans (ESKAPEE). Using transcriptomics, candidate AMPs were detected in all individuals with Cathelidicins being most common. Using proteomics, AMPs were found in 34% of individuals (31/91)—predominately E. bislineata—with Kinin-like peptides being most common. Candidate AMP composition generally predicted skin bacterial composition, suggesting that AMPs influence host-microbial symbioses. Crude and synthesized peptides showed limited activity against Bd. Two synthesized Cathelicidins (Pcin-CATH3 and Pcin-CATH5) inhibited human pathogens, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli. Our findings inform the potential usage of AMPs in conservation and translational applications.