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Antimicrobial Agents and Chemotherapy, April 2007, p. 1351-1358, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01270-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Novel Synthetic Antimicrobial Peptides against Streptococcus mutans{triangledown}

Jian He,1,{dagger} Randal Eckert,2,{dagger} Thanh Pharm,2 Maurice D. Simanian,2 Chuhong Hu,1 Daniel K. Yarbrough,1 Fengxia Qi,1 Maxwell H. Anderson,3 and Wenyuan Shi1,2*

School of Dentistry,1 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095,2 C3 Jian, Inc., Sequim, Washington 983823

Received 11 October 2006/ Returned for modification 7 December 2006/ Accepted 1 February 2007

Streptococcus mutans, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against S. mutans. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these "fusion" peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against S. mutans, several of which may be likely candidates for the development of anticaries agents.

* Corresponding author. Mailing address: UCLA School of Dentistry, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668. Phone: (310) 825-8356. Fax: (310) 794-7109. E-mail: wenyuan{at}ucla.edu

{triangledown} Published ahead of print on 12 February 2007.

{dagger} These authors contributed equally to this report.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1351-1358, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01270-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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