Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity.
Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 μg ml(-1) mPE was sufficient to inhibit interleukin-1β-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-κB, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues.
Department of Oral Biology, UMDNJ-New Jersey Dental School, Newark, NJ 07103, USA.
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Hua
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Scott
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Diamond
D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects*; D000480:Alkynes / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D058491:Bacterial Load; D018441:Biofilms / Q000187:drug effects*; D040761:Biomimetic Materials / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000494:pharmacology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D016209:Interleukin-8 / Q000037:antagonists & inhibitors; D015603:Keratinocytes / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010510:Periodontal Diseases / Q000382:microbiology*; D010627:Phenethylamines / Q000494:pharmacology*; D016966:Porphyromonas gingivalis / Q000187:drug effects*
D000480:Alkynes; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D010627:Phenethylamines; C525734:meta-phenylene ethynylene