Immunogenic epitope scanning in bacteriolytic enzymes Pal and Cpl-1 and engineering Pal to escape antibody responses

Bacteriolytic enzymes are promising antibacterial agents, but they can cause a typical immune response in vivo . In this study, we used targeted modification method for two endolysins, Pal and Cpl-1. We identified the key immunogenic amino acids, designed tested new, bacteriolytic variants with altered immunogenicity. One new variant of (257-259 MKS → TFG) demonstrated decreased immunogenicity while similar mutant TFK) increased A third (280-282 DKP GGA) significantly activity it was not cross-neutralized by antibodies induced wild-type enzyme. propose as engineered endolysin that is capable escaping cross-neutralization Pal. show efficient avoid IgG be developed epitope scanning, silico design, substitutions acids high rate success. Importantly, universal approach applied to many proteins beyond endolysins has potential design numerous biological drugs.