Targeting Intracellular Pathogenic Bacteria with Unnatural Proline‐Rich Peptides: Coupling Antibacterial Activity with Macrophage Penetration

De novo design of unnatural proline-rich peptides led to a potent antibacterial peptide that targets both Gram-positive and -negative bacteria. The peptide exerts activity without lysing bacterial membranes or causing hemolysis, and is stable to extended trypsin treatment. Facile entry into macrophages was observed, leading to extensive intracellular clearing of pathogenic bacteria.