ESKtides: a comprehensive database and mining method for ESKAPE phage-derived antimicrobial peptides

'Superbugs' have received increasing attention from researchers, such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), which directly led to about 1 270 000 death cases in 2019. Recently, phage peptidoglycan hydrolases (PGHs)-derived antimicrobial peptides were proposed as new antibacterial agents against multidrug-resistant bacteria. However, there is still a lack of methods for mining antimicrobial peptides based on phages or phage PGHs. Here, by using a collection of 6809 genomes of ESKAPE isolates and corresponding phages in public databases, based on a unified annotation process of all the genomes, PGHs were systematically identified, from which peptides were mined. As a result, a total of 12 067 248 peptides with high antibacterial activities were respectively determined. A user-friendly tool was developed to predict the phage PGHs-derived antimicrobial peptides from customized genomes, which also allows the calculation of peptide phylogeny, physicochemical properties, and secondary structure. Finally, a user-friendly and intuitive database, ESKtides (http://www.phageonehealth.cn:9000/ESKtides), was designed for data browsing, searching and downloading, which provides a rich peptide library based on ESKAPE prophages and phages.Database URL: 10.1093/database/baae022