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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Produce Safety and Microbiology Research » Research » Publications at this Location » Publication #276502
Title: Genome sequence of E. coli O104:H4 leads to rapid development of a targeted antimicrobial agent against this emerging pathogen.

Author
item SCHOLL, DEAN - Avidbiotics Corporation
item GEBHART, DANA - Avidbiotics Corporation
item WILLIAMS, STEVEN - Avidbiotics Corporation
item Bates, Anne
item Mandrell, Robert

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/17/2012
Publication Date: 3/14/2012
Citation: Scholl, D., Gebhart, D., Williams, S., Bates, A.H., Mandrell, R.E. 2012. Genome sequence of E. coli O104:H4 leads to rapid development of a targeted antimicrobial agent against this emerging pathogen. PLoS One. 7(3):e33637.doi:10.1371/journal.pone.0033637.

Interpretive Summary: A recent widespread outbreak of Escherichia coli O104:H4 in Germany caused >4000 illnesses, 50 deaths and hundreds of cases of severe kidney disease as a result of a virulent toxin and other virulence factors. This outbreak emphasizes the dynamic nature of emerging and re-emerging food-borne pathogens, particularly STECs and related pathogenic E. coli. The genomic sequence data that was made available to the public rapidly allowed identification of a protein encoded in the genome that could be used to potentially kill the outbreak strain and other strains with a similar outer surface sugar structure. The gene encoding the protein was synthesized and used to construct a DNA sequence that could be used in E. coli bacteria to make the killing protein, which is a type of bacteriocin. The resulting protein particles can kill specific E. coli strains that produce the outbreak strain surface structure made of carbohydrate. This strategy provides a platform to respond rapidly to emerging pathogens upon the availability of the pathogen’s genome sequence.

Technical 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 genomic 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 tail spike-R-type pyocin strategy provides a platform to respond rapidly to emerging pathogens upon the availability of the pathogen’s genome sequence.