Abstract
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 μg/ml, CLP-4 completely inhibited S. mutans UA159 biofilm formation, and at 50 μg/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.
| Original language | English (US) |
|---|---|
| Article number | e00776 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 61 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2017 |
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Keywords
- Antimicrobial peptide
- Cyclic lipopeptide
- Dental biofilms
- Dental plaque
- Streptococcus mutans
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
Cite this
Antibacterial and antibiofilm activities of a novel synthetic cyclic lipopeptide against cariogenic Streptococcus mutans UA159. / Min, Kyung R.; Galvis, Adriana; Williams, Brandon; Rayala, Ramanjaneyulu; Cudic, Predrag; Ajdic, Dragana.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 8, e00776, 01.08.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antibacterial and antibiofilm activities of a novel synthetic cyclic lipopeptide against cariogenic Streptococcus mutans UA159
AU - Min, Kyung R.
AU - Galvis, Adriana
AU - Williams, Brandon
AU - Rayala, Ramanjaneyulu
AU - Cudic, Predrag
AU - Ajdic, Dragana
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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 μg/ml, CLP-4 completely inhibited S. mutans UA159 biofilm formation, and at 50 μg/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.
AB - 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 μg/ml, CLP-4 completely inhibited S. mutans UA159 biofilm formation, and at 50 μg/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.
KW - Antimicrobial peptide
KW - Cyclic lipopeptide
KW - Dental biofilms
KW - Dental plaque
KW - Streptococcus mutans
UR - http://www.scopus.com/inward/record.url?scp=85026377852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026377852&partnerID=8YFLogxK
U2 - 10.1128/AAC.00776-17
DO - 10.1128/AAC.00776-17
M3 - Article
C2 - 28533236
AN - SCOPUS:85026377852
VL - 61
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 8
M1 - e00776
ER -