RESUMO
INTRODUCTION: Cathelicidins are antimicrobial peptides found in epithelial and mucosal tissues as well as the secondary granules of neutrophils. SMAP29, a sheep cathelicidin, has differential antimicrobial properties against various pathogens, including periodontal organisms. The purpose of this study was to evaluate the antimicrobial properties and cytotoxicity of SMAP29, SMAP28, and three congeners (SMAP18A, SMAP18D, and SMAP14A). METHODS: The peptides at concentrations ranging from 0.25 to 250 microg/ml were tested for their activity against multiple strains of Streptococcus mutans, Streptococcus sanguis, Actinomyces israelii, Actinomyces naeslundii, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Peptostreptococcus micros, and Porphyromonas gingivalis using a radial diffusion assay. Cytotoxicity of keratinocytes was evaluated by measuring lactate dehydrogenase release after incubation with the individual peptides. RESULTS: SMAP28, thought to be the biologically active peptide, was the most potent antimicrobial (range of minimum inhibitory concentrations 0.06-7.03 microg/ml, P < 0.05); however, the activity of SMAP28 and SMAP29 was strongly associated (r = 0.933). The congeners also demonstrated antimicrobial activity against the bacteria tested (range of minimum inhibitory concnetrations 0.21-79 microg/ml). Overall, F. nucleatum was the most susceptible organism, while P. gingivalis was the least susceptible. Keratinocyte cytotoxicity was dependent on peptide length and dose. SMAP28 was the most cytotoxic, while SMAP14A was the least cytotoxic. CONCLUSION: The antimicrobial activities against oral microorganisms and the minimal toxicity seen in this study suggest that the congeners of SMAP29 may serve as an alternative to traditional antibiotics in the prevention and treatment of periodontal and other oral diseases.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Proteínas Sanguíneas/farmacologia , Catelicidinas/farmacologia , Gengiva/efeitos dos fármacos , Actinomyces/efeitos dos fármacos , Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos/toxicidade , Proteínas Sanguíneas/toxicidade , Catelicidinas/toxicidade , Fusobacterium nucleatum/efeitos dos fármacos , Gengiva/citologia , Humanos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Peptostreptococcus/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Carneiro Doméstico , Streptococcus/efeitos dos fármacosRESUMO
The effects of cathelicidins against oral bacteria and clinically important oral yeasts are not known. We tested the susceptibilities of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus sanguis, Candida krusei, Candida tropicalis and Candida albicans to the following cathelicidins: FALL39, SMAP29, and CAP18. SMAP29 and CAP18 were antimicrobial, whereas FALL39 did not exhibit antimicrobial activity. Future studies are needed to determine the potential use of these antimicrobial peptides in prevention and treatment of oral infections.