Antibacterial and Antibiofilm Activities of a Novel Synthetic Cyclic Lipopeptide against Cariogenic Streptococcus mutans UA159

作者：Min Kyung R; Galvis Adriana; Williams Brandon; Rayala Ramanjaneyulu; Cudic Predrag; Ajdic Dragana^*

来源：Antimicrobial Agents and Chemotherapy, 2017, 61(8): e00776-17.

DOI：10.1128/AAC.00776-17

• Streptococcus mutans
• antimicrobial peptide
• cyclic lipopeptide
• dental biofilms
• dental plaque

Despite continuous efforts to control cariogenic dental biofilms, very few effective antimicrobial treatments exist. In this study, we characterized the activity of the novel synthetic cyclic lipopeptide 4 (CLP-4), derived from fusaricidin, against the cariogenic pathogen Streptococcus mutans UA159. We determined CLP-4' s MIC, minimum bactericidal concentration (MBC), and spontaneous resistance frequency, and we performed time-kill assays. Additionally, we assessed CLP-4' s potential to inhibit biofilm formation and eradicate preformed biofilms. Our results demonstrate that CLP-4 has strong antibacterial activity in vitro and is a potent bactericidal agent with low spontaneous resistance frequency. At a low concentration of 5 mu g/ml, CLP-4 completely inhibited S. mutans UA159 biofilm formation, and at 50 mu g/ml, it reduced the viability of established biofilms by >99.99%. We also assessed CLP-4' s cytotoxicity and stability against proteolytic digestion. CLP-4 withstood trypsin or chymotrypsin digestion even after treatment for 24 h, and our toxicity studies showed that CLP-4 effective concentrations had negligible effects on hemolysis and the viability of human oral fibroblasts. In summary, our findings showed that CLP-4 is a potent antibacterial and antibiofilm agent with remarkable stability and low nonspecific cytotoxicity. Hence, CLP-4 is a promising novel antimicrobial peptide with potential for clinical application in the prevention and treatment of dental caries.

• 出版日期2017-8