A VersaTile-driven platform for rapid hit-to-lead development of engineered lysins.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32537492.
- Also identified by DOI 10.1126/sciadv.aaz1136 and PMC identifier 7269649.
- Licence recorded as CC BY-NC.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Health care authorities are calling for new antibacterial therapies to cope with the global emergence of antibiotic-resistant bacteria. Bacteriophage-encoded lysins are a unique class of antibacterials with promising (pre)clinical progress. Custom engineering of lysins allows for the creation of variants against potentially any bacterial pathogen. We here present a high-throughput hit-to-lead development platform for engineered lysins. The platform is driven by VersaTile, a new DNA assembly method for the rapid construction of combinatorial libraries of engineered lysins. We constructed approximately 10,000 lysin variants. Using an iterative screening procedure, we identified a lead variant with high antibacterial activity against <i>Acinetobacter baumannii</i> in human serum and an ex vivo pig burn wound model. This generic platform could offer new opportunities to populate the preclinical pipeline with engineered lysins for diverse (therapeutic) applications.