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Antimicrobial Agents and Chemotherapy, July 2009, p. 3074-3080, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01660-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

An Engineered R-Type Pyocin Is a Highly Specific and Sensitive Bactericidal Agent for the Food-Borne Pathogen Escherichia coli O157:H7{triangledown} ,{dagger}

Dean Scholl,1* Mike Cooley,2 Steve R. Williams,1 Dana Gebhart,1 David Martin,1 Anna Bates,2 and Robert Mandrell2

AvidBiotics Corporation, 300 Utah Avenue, South San Francisco, CA 94080,1 U.S. Department of Agriculture, Agricultural Research Service, Western Regional Research Center, Produce Safety and Microbiology Unit, 800 Buchanan Street, Albany, California 947102

Received 17 December 2008/ Returned for modification 30 January 2009/ Accepted 27 March 2009

Some strains of Pseudomonas aeruginosa produce R-type pyocins, which are high-molecular-weight phage tail-like protein complexes that have bactericidal activity against other Pseudomonas strains. These particles recognize and bind to bacterial surface structures via tail fibers, their primary spectrum determinant. R-type pyocins kill the cell by contracting a sheath-like structure and inserting their hollow core through the cell envelope, resulting in dissipation of the cellular membrane potential. We have retargeted an R-type pyocin to Escherichia coli O157:H7 by fusing a tail spike protein from an O157-specific phage, {phi}V10, to the pyocin tail fiber. The {phi}V10 tail spike protein recognizes and degrades the O157 lipopolysaccharide. This engineered pyocin, termed AVR2-V10, is sensitive and specific, killing 100% of diverse E. coli O157:H7 isolates but no other serotypes tested. AVR2-V10 can kill E. coli O157:H7 on beef surfaces, making it a candidate agent for the elimination of this pathogen from food products. All rare AVR2-V10-resistant mutants isolated and examined have lost the ability to produce the O157 antigen and are expected to have compromised virulence. In addition, E. coli O157:H7 exposed to and killed by AVR2-V10 do not release Shiga toxin, as is often the case with many antibiotics, suggesting potential therapeutic applications. The demonstration that a novel R-type pyocin can be created in the laboratory by fusing a catalytic tail spike from the family Podoviridae to a tail fiber of a member of the family Myoviridae is evidence that the plasticity observed among bacteriophage tail genes can, with modern molecular techniques, be exploited to produce nonnatural, targeted antimicrobial agents.

* Corresponding author. Mailing address: AvidBiotics Corporation, 300 Utah Avenue, South San Francisco, CA 94080. Phone: (650) 873-1117. Fax: (650) 873-1010. E-mail: dean{at}avidbiotics.com

{triangledown} Published ahead of print on 6 April 2009.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, July 2009, p. 3074-3080, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01660-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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