| 1097 Antimicrobial Activity of Peptide-Mimetics Against Biofilm Cultures of Oral Pathogens | ||
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N. BECKLOFF1, D. LAUBE1, T. CASTRO1, D. FURGANG1, D. LIU2, R.W. SCOTT2, G.N. TEW3, W.F. DEGRADO4, and G. DIAMOND1, 1UMDNJ-New Jersey Dental School, Newark, USA, 2Polymedix Inc, Bryn Mawr, PA, USA, 3University of Massachusetts, Amherst, USA, 4University of Pennsylvania, School of Medicine, Philadelphia, USA Innate immunity is anchored by broad-spectrum antimicrobial peptides (AMPs) that target membrane structures of bacterial cells resulting in cell lysis. Physical hallmarks of these peptides include cationic charge and mixtures of -helical and -sheet structures. Bacterial resistance to these peptides does not occur making them potentially useful as antibiotics. However, their development as therapeutic antimicrobials is hampered by their sensitivity to protease digestion and expense in production. The quest for new and improved antimicrobial peptides has led to the field of peptide mimetics that has developed a series of inexpensive nonpeptidic oligomers and polymers that mimic AMPs in both structure and antimicrobial activity, with low hemolytic activity. Furthermore, these small molecules may more easily penetrate complex microbial structures such as biofilms. Objective: To characterize the activity of a class of peptide mimetics against oral pathogens growing in planktonic and biofilm cultures. Methods: We performed standard liquid antimicrobial assays in several types of media to determine the minimum inhibitory concentration (MIC) and kinetics of killing of planktonic Streptococcus mutans (Sm) and Porphryromas gingivalis (Pg). For biofilm assays, Sm was grown in 10% sucrose to encourage the formation of biofilm, followed by, or simultaneous with, incubation with antimicrobial agents. Microbicidal effects were quantified based on recovered viable bacteria. Results: We demonstrate that the compounds exhibited MICs for planktonic Sm from 1.5µg/ml to less than 0.78µg/ml. Pmx70004 exhibited significant bacteriostatic and bacteriocidal activity against biofilms of Sm when added before, 0.3-0.6 μg/mL, and after, 2.5-5 μg/mL, establishment. Conclusion: This class of peptide-mimetic may be useful in preventing and treating a wide range of oral infections, including those that persist in biofilms. Supported by Polymedix, Inc and NIH R01 DE1487.
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| Seq #138 - Microbiology/Immunology of Periodontal Diseases 2:00 PM-3:00 PM, Friday, 10 March 2006 Dolphin Hotel Pacific Hall | ||
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