title: Genome sequence of E. coli O104:H4 leads to rapid development of a targeted antimicrobial agent against this emerging pathogen.
abstract: A recent widespread outbreak of Escherichia coli O104:H4 in Germany demonstrates the dynamic nature of emerging and re-emerging food-borne pathogens, particularly STECs and related pathogenic E. coli. Rapid genome sequencing and public availability of these data from the German outbreak strain allowed us to identify an O-antigen-specific bacteriophage tail spike protein encoded in the genome. We synthesized this gene and fused it to the tail fiber gene of an R-type pyocin, a phage tail-like bacteriocin, and expressed the novel bacteriocin such that the tail fiber fusion was incorporated into the bacteriocin structure. The resulting particles have bactericidal activity specifically against E. coli strains that produce the O104 lipopolysaccharide antigen, including the outbreak strain. This O-antigen tailspike-R-type pyocin strategy provides a platform to respond rapidly to emerging pathogens upon the availability of the pathogen's genome sequence.
authors.affiliation: AvidBiotics Corporation, South San Francisco, California, United States of America. dean@avidbiotics.com
authors.forename: Dean
authors.initials: D
authors.lastname: Scholl
authors.forename: Dana
authors.initials: D
authors.lastname: Gebhart
authors.forename: Steven R
authors.initials: SR
authors.lastname: Williams
authors.forename: Anna
authors.initials: A
authors.lastname: Bates
authors.forename: Robert
authors.initials: R
authors.lastname: Mandrell
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D016680:Genome, Bacterial / Q000235:genetics*; D008070:Lipopolysaccharides / Q000302:isolation & purification; D009154:Mutation / Q000235:genetics; D016622:Silver Staining
chemical_list: D000890:Anti-Infective Agents; D008070:Lipopolysaccharides