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Antimicrobial Agents and Chemotherapy, May 2008, p. 1647-1652, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01479-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antibacterial Efficacy of R-Type Pyocins towards Pseudomonas aeruginosa in a Murine Peritonitis Model{triangledown}

Dean Scholl* and David W. Martin Jr.

AvidBiotics Corp., South San Francisco, California

Received 14 November 2007/ Returned for modification 24 January 2008/ Accepted 4 March 2008

R-type pyocins are high-molecular-weight bacteriocins carried within the chromosomes of some bacterial species, such as Pseudomonas aeruginosa, and almost certainly evolved from lysogenic bacteriophages of the Myoviridae family. They contain no head structures and no DNA and are used as defense systems, usually against other strains of the same bacterial species. They bind with their tail fibers to targeted bacterial surface molecules and then kill by inserting a core or needle that dissipates the bacterial membrane potential. Their mechanism of action, high bactericidal potency (one pyocin particle can kill one bacterium), and focused spectrum suggest that R-type pyocins could be developed as antibacterial agents. In a lethal mouse peritonitis model, submicrogram quantities of pyocin prevent death from 90% lethal dose inocula of a pyocin-sensitive, clinical isolate of P. aeruginosa. We show here the dose response curves, treatment windows, or periods of response after infection and the several-log-unit acute reduction of bacterial load in blood and spleen samples, suggesting that R-type pyocins have several characteristics that one would expect from an effective therapeutic.

* Corresponding author. Mailing address: AvidBiotics, 385 Oyster Point Blvd., Suite 6A, South San Francisco, CA 94080-1970. Phone: (650) 873-1117. Fax: (650) 873-1010. E-mail: dean{at}avidbiotics.com

{triangledown} Published ahead of print on 10 March 2008.

Antimicrobial Agents and Chemotherapy, May 2008, p. 1647-1652, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01479-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Scholl, D., Cooley, M., Williams, S. R., Gebhart, D., Martin, D., Bates, A., Mandrell, R. (2009). An Engineered R-Type Pyocin Is a Highly Specific and Sensitive Bactericidal Agent for the Food-Borne Pathogen Escherichia coli O157:H7. Antimicrob. Agents Chemother. 53: 3074-3080 [Abstract] [Full Text]  
  • Heo, Y.-J., Lee, Y.-R., Jung, H.-H., Lee, J., Ko, G., Cho, Y.-H. (2009). Antibacterial Efficacy of Phages against Pseudomonas aeruginosa Infections in Mice and Drosophila melanogaster. Antimicrob. Agents Chemother. 53: 2469-2474 [Abstract] [Full Text]  
  • Williams, S. R., Gebhart, D., Martin, D. W., Scholl, D. (2008). Retargeting R-Type Pyocins To Generate Novel Bactericidal Protein Complexes. Appl. Environ. Microbiol. 74: 3868-3876 [Abstract] [Full Text]  


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