Beschreibung:
<jats:title>Significance</jats:title>
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Apidaecin (Api) is a ribosome-targeting proline-rich antimicrobial peptide with a unique mechanism of action. Api’s activity against Gram-negative pathogens makes it an attractive candidate for developing new antibiotics. The approaches based on analyzing the antibacterial activity of chemically synthesized peptides fail to distinguish the effects upon cellular uptake from those affecting the on-target activity. By expressing a comprehensive library of
<jats:italic>api</jats:italic>
gene mutants in the bacterial cell and analyzing the library composition by next-generation sequencing, we identified in a single experiment the on-target activity of every single-amino-acid mutant. Location of the inactivating mutations defined the peptide’s pharmacophore, which is confined to five C-terminal residues. Identification of mutations preserving activity delineated the sequence space available for modifying the peptide’s antibiotic properties.
</jats:p>