Deep Antimicrobial Activity and Stability Analysis Inform Lysin Sequence-Function Mapping.

ABSTRACT: Antibiotic-resistant infectious disease is a critical challenge to human health. Antimicrobial proteins offer a compelling solution if engineered for potency, selectivity, and physiological stability. Lysins, which lyse cells via degradation of cell wall peptidoglycans, have significant potential to fill this role. Yet, the functional complexity of antimicrobial activity has hindered high-throughput characterization for discovery and design. To dramatically expand knowledge of the sequence-function landscape of lysins, we developed a depletion-based assay for library-scale measurement of lysin inhibitory activity. We coupled this platform with a high-throughput proteolytic stability assay to assess the activity and stability of ∼5 × 10⁴ lysin catalytic domain variants, resulting

SUBMITTER: Tresnak DT 

PROVIDER: S-EPMC10822705 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature