Structure-based redesign of lysostaphin yields potent antistaphylococcal enzymes that evade immune cell surveillance.

ABSTRACT: Staphylococcus aureus infections exert a tremendous burden on the health-care system, and the threat of drug-resistant strains continues to grow. The bacteriolytic enzyme lysostaphin is a potent antistaphylococcal agent with proven efficacy against both drug-sensitive and drug-resistant strains; however, the enzyme's own bacterial origins cause undesirable immunogenicity and pose a barrier to clinical translation. Here, we deimmunized lysostaphin using a computationally guided process that optimizes sets of mutations to delete immunogenic T cell epitopes without disrupting protein function. In vitro analyses showed the methods to be both efficient and effective, producing seven different deimmunized designs exhibiting high function and reduced immunogenic potential. Two deimmunized candida

SUBMITTER: Blazanovic K 

PROVIDER: S-EPMC4470366 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature