Antibacterial and antibiofilm activities of a novel synthetic cyclic lipopeptide against cariogenic Streptococcus mutans UA159

Kyung R. Min, Adriana Galvis, Brandon Williams, Ramanjaneyulu Rayala, Predrag Cudic, Dragana Ajdic

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
Article numbere00776
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Lipopeptides
Streptococcus mutans
Biofilms
Digestion
Dental Caries
Hemolysis
Tooth
Fibroblasts
Anti-Bacterial Agents
Peptides

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 journalArticle

Min, Kyung R. ; Galvis, Adriana ; Williams, Brandon ; Rayala, Ramanjaneyulu ; Cudic, Predrag ; Ajdic, Dragana. / Antibacterial and antibiofilm activities of a novel synthetic cyclic lipopeptide against cariogenic Streptococcus mutans UA159. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 8.
@article{90267ef2917d4003a61fe2632b0eced1,
title = "Antibacterial and antibiofilm activities of a novel synthetic cyclic lipopeptide against cariogenic Streptococcus mutans UA159",
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.",
keywords = "Antimicrobial peptide, Cyclic lipopeptide, Dental biofilms, Dental plaque, Streptococcus mutans",
author = "Min, {Kyung R.} and Adriana Galvis and Brandon Williams and Ramanjaneyulu Rayala and Predrag Cudic and Dragana Ajdic",
year = "2017",
month = "8",
day = "1",
doi = "10.1128/AAC.00776-17",
language = "English (US)",
volume = "61",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "8",

}

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 -