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Colicin E9 is a plasmid-encoded, DNase-type bacteriocin (protein antibiotic) naturally produced by *Escherichia coli* strains to kill competing bacteria. It consists of three functional domains: a central receptor-binding domain that targets the outer membrane vitamin B12 transporter BtuB, an N-terminal translocation domain that recruits the outer membrane porin OmpF (or OmpC) and interacts with the periplasmic protein TolB to facilitate translocation across the cell envelope, and a C-terminal cytotoxic endonuclease (DNase) domain. Once inside the cytoplasm of target Gram-negative bacteria, the DNase domain enzymatically cleaves chromosomal DNA, leading to cell death. In addition to its bactericidal properties, colicin E9 is being investigated preclinically as an antivirulence agent against multidrug-resistant pathogens, such as ESBL-producing *Klebsiella pneumoniae*, where it has been shown to reduce biofilm formation and capsule expression without necessarily killing the bacteria, thereby minimizing selective pressure for resistance.
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