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Antimicrobial Agents and Chemotherapy, June 2006, p. 2087-2097, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00169-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Targeting Antibacterial Agents by Using Drug-Carrying Filamentous Bacteriophages

Iftach Yacoby,1 Marina Shamis,2 Hagit Bar,1 Doron Shabat,2 and Itai Benhar1*

Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences,1 Department of Organic Chemistry, School of Chemistry, Tel-Aviv University, Ramat Aviv 69978, Israel2

Received 8 February 2006/ Returned for modification 23 March 2006/ Accepted 31 March 2006

Bacteriophages have been used for more than a century for (unconventional) therapy of bacterial infections, for half a century as tools in genetic research, for 2 decades as tools for discovery of specific target-binding proteins, and for nearly a decade as tools for vaccination or as gene delivery vehicles. Here we present a novel application of filamentous bacteriophages (phages) as targeted drug carriers for the eradication of (pathogenic) bacteria. The phages are genetically modified to display a targeting moiety on their surface and are used to deliver a large payload of a cytotoxic drug to the target bacteria. The drug is linked to the phages by means of chemical conjugation through a labile linker subject to controlled release. In the conjugated state, the drug is in fact a prodrug devoid of cytotoxic activity and is activated following its dissociation from the phage at the target site in a temporally and spatially controlled manner. Our model target was Staphylococcus aureus, and the model drug was the antibiotic chloramphenicol. We demonstrated the potential of using filamentous phages as universal drug carriers for targetable cells involved in disease. Our approach replaces the selectivity of the drug itself with target selectivity borne by the targeting moiety, which may allow the reintroduction of nonspecific drugs that have thus far been excluded from antibacterial use (because of toxicity or low selectivity). Reintroduction of such drugs into the arsenal of useful tools may help to combat emerging bacterial antibiotic resistance.

* Corresponding author. Mailing address: Green Building Room 202, Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Ramat Aviv 69978, Israel. Phone: 972-3-6407511. Fax: 972-3-6409407. E-mail: benhar{at}post.tau.ac.il.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2087-2097, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00169-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yacoby, I., Bar, H., Benhar, I. (2007). Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines. Antimicrob. Agents Chemother. 51: 2156-2163 [Abstract] [Full Text]  


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