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Antimicrobial Agents and Chemotherapy, November 2007, p. 4125-4132, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00208-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Activity of an Antimicrobial Peptide Mimetic against Planktonic and Biofilm Cultures of Oral Pathogens ^,

Nicholas Beckloff,¹ Danielle Laube,¹ Tammy Castro,^1,5 David Furgang,¹ Steven Park,² David Perlin,² Dylan Clements,³ Haizhong Tang,³ Richard W. Scott,³ Gregory N. Tew,⁴ and Gill Diamond^1*

Department of Oral Biology, UMDNJ-New Jersey Dental School, Newark, New Jersey 07101,¹ Public Health Research Institute, Newark, New Jersey 07101,² Polymedix, Inc., Radnor, Pennsylvania 19087,³ Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003,⁴ Division of Natural Sciences and Mathematics, Bloomfield College, Bloomfield, New Jersey 07003⁵

Received 12 February 2007/ Returned for modification 13 April 2007/ Accepted 26 August 2007

Antimicrobial peptides (AMPs) are naturally occurring, broad-spectrum antimicrobial agents that have recently been examined for their utility as therapeutic antibiotics. Unfortunately, they are expensive to produce and are often sensitive to protease digestion. To address this problem, we have examined the activity of a peptide mimetic whose design was based on the structure of magainin, exhibiting its amphiphilic structure. We demonstrate that this compound, meta-phenylene ethynylene (mPE), exhibits antimicrobial activity at nanomolar concentrations against a variety of bacterial and Candida species found in oral infections. Since Streptococcus mutans, an etiological agent of dental caries, colonizes the tooth surface and forms a biofilm, we quantified the activity of this compound against S. mutans growing under conditions that favor biofilm formation. Our results indicate that mPE can prevent the formation of a biofilm at nanomolar concentrations. Incubation with 5 nM mPE prevents further growth of the biofilm, and 100 nM mPE reduces viable bacteria in the biofilm by 3 logs. Structure-function analyses suggest that mPE inhibits the bioactivity of lipopolysaccharide and binds DNA at equimolar ratios, suggesting that it may act both as a membrane-active molecule, similar to magainin, and as an intracellular antibiotic, similar to other AMPs. We conclude that mPE and similar molecules display great potential for development as therapeutic antimicrobials.

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* Corresponding author. Mailing address: Department of Oral Biology, UMDNJ-New Jersey Dental School, 185 South Orange Ave., Newark, NJ 07103. Phone: (973) 972-3324. Fax: (973) 972-0045. E-mail: gdiamond{at}umdnj.edu

Published ahead of print on 4 September 2007.

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

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Antimicrobial Agents and Chemotherapy, November 2007, p. 4125-4132, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00208-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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