Antimicrobial and anti-biofilm effect of Bac8c on major bacteria associated with dental caries and Streptococcus mutans biofilms

Ding, Yue; Wang, Wei; Fan, Meng; Tong, Zhongchun; Kuang, Rongze; Jiang, Wenkai; Ni, Longxing

doi:10.1016/j.peptides.2013.11.020

Cited by 69 publications

(49 citation statements)

References 30 publications

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“…Nevertheless, up til now, for AMPs, there has been little literature about their anti-virulence activities against S. mutans . Prior to our study, only that on Bac8c [17] reported limited information on its inhibition of the GTF gene expression at two-fold MBC against S. mutans . Thus, to our knowledge, this is the first time to systematically investigate effects of AMPs on virulence and regulatory systems of S. mutans .…”

Section: Discussionmentioning

confidence: 99%

“…Over the last decade, a significant leap in studies about control of oral pathogens by AMPs was observed [13]. So far, many natural or synthetic AMPs have shown inhibitory effects on growth of planktonic cells and biofilm of S. mutans in vitro , including defensins, Cathelicidin LL-37, Histatin 5, Human Lactoferrin [14], KSL [15], L-K6 [16], Bac8c [17], and C16G2 [18]. Furthermore, the placebo-controlled clinical data of C16G2 rinse showed this AMP was safe and reduced S. mutans and enamel demineralization [19].…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Wang

Jiang

et al. 2018

Journal of Oral Microbiology

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Cariogenic virulence factors of Streptococcus mutans include acidogenicity, aciduricity, and extracellular polysaccharides (EPS) synthesis. The de novo designed antimicrobial peptide GH12 has shown bactericidal effects on S. mutans, but its interaction with virulence and regulatory systems of S. mutans remains to be elucidated. The objectives were to investigate the effects of GH12 on virulence factors of S. mutans, and further explore the function mechanisms at enzymatic and transcriptional levels. To avoid decrease in bacterial viability, we limited GH12 to subinhibitory levels. We evaluated effects of GH12 on acidogenicity of S. mutans by pH drop, lactic acid measurement and lactate dehydrogenase (LDH) assay, on aciduricity through survival rate at pH 5.0 and F1F0-ATPase assay, and on EPS synthesis using quantitative measurement, morphology observation, vertical distribution analyses and biomass calculation. Afterwards, we conducted quantitative real-time PCR to acquire the expression profile of related genes. GH12 at 1/2 MIC (4 mg/L) inhibited acid production, survival rate, EPS synthesis, and biofilm formation. The enzymatic activity of LDH and F1F0-ATPase was inhibited, and ldh, gtfBCD, vicR, liaR, and comDE genes were significantly downregulated. In conclusion, GH12 inhibited virulence factors of S. mutans, through reducing the activity of related enzymes, downregulating virulence genes, and inactivating specific regulatory systems.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Wang

Jiang

et al. 2018

Journal of Oral Microbiology

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“…The rapid activity of GH12 is important for clinical applications, since the typical duration of oral rinsing is 0.5-2 min. Rapid action is also important if the peptide is applied at home as a component of toothpaste, in which case contact time may be only 2-5 min [Ding et al, 2014]. The rapid activity of GH12 in vitro increases its potential for practical applications.…”

Section: Discussionmentioning

confidence: 99%

Activity of Synthetic Antimicrobial Peptide GH12 against Oral Streptococci

Fan²,

Lv³

et al. 2016

Caries Res

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Controlling the growth of cariogenic microorganisms such as oral streptococci is an adjunct therapy for caries-active individuals to prevent and treat caries. Here we investigated the antimicrobial activity of the synthetic amphipathic α- helical antimicrobial peptide GH12 (GLLWHLLHHLLH-NH₂) against oral streptococci in vitro. Circular dichroism studies showed that GH12 takes on an α-helical conformation in the presence of membrane-mimicking solvents, and reversed-phase high-performance liquid chromatography studies showed that GH12 remains stable in saliva. The peptide showed bactericidal activity against oral streptococci, with minimum inhibitory concentrations ranging from 6.7 to 32.0 μg/ml. GH12 concentrations 4-fold higher than the minimum bactericidal concentration completely killed oral streptococci within 20 min. Treating oral streptococci with GH12 caused noticeable changes in bacterial viability and morphology based on confocal laser scanning microscopy and scanning electron microscopy. Effects of GH12 on biofilm formation and on viability of mature biofilm were quantified by crystal violet staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. GH12 effectively inhibited biofilm formation and metabolic activity in biofilms of oral streptococci, especially S. mutans, S. sobrinus and S. salivarius. These results suggest that GH12 shows rapid and strong antimicrobial activity against oral streptococci in vitro, opening the door to preclinical and clinical studies to explore its potential for caries prevention and treatment.

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“…The killing kinetics of the AMP against S. mutans was analyzed using a time-kill assay as previously described [Ding et al, 2014]. The method in this study was modified as follows.…”

Section: Time-killing Assaymentioning

confidence: 99%

“…It has also been reported that combinations of a traditional antibiotic and AMPs can be effective as antimicrobial agents against oral pathogens [Lobos et al, 2009]. Recently, the number of synthetic AMPs has increased in the field of oral diseases, especially those directed against S. mutans [Ding et al, 2014;Min et al, 2017]. In addition, specific or selectively targeted AMPs have been designed as structural AMPs that combine an S. mutans-targeting domain with a killing domain [Eckert et al, 2006;He et al, 2010;Mai et al, 2011].…”

mentioning

confidence: 99%

A Membrane-Targeted Peptide Inhibiting PtxA of Phosphotransferase System Blocks <b><i>Streptococcus mutans</i></b>

Xiang

Shao

et al. 2018

Caries Res

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Streptococcus mutans, the primary cause of dental caries, takes up carbohydrates through the phosphoenolpyruvate sugar phosphotransferase system (PTS). This study aimed to identify a novel membrane-targeted antimicrobial peptide (AMP) that could also target the L-ascorbate-specific PtxA component of the S. mutans PTS system. C10-KKWW was identified and selected using virtual screening of a lipopeptide library, a minimum inhibiting concentration (MIC) assay, cytotoxicity assays and a hemolysis assay. Surface plasmon resonance confirmed that C10-KKWW had a high binding affinity for PtxA. Combining with scanning electron microscopy and cell permeability assay, it was shown that the effects of C10-KKWW could be attributed to both membrane and PtxA. Wild type (WT) S. mutans, a ptxA deletion mutant (ΔptxA), and a mutant-complemented strain (CptxA), were cultured consistently in brain heart infusion (BHI) medium, tryptone-vitamin medium supplemented with 15 mM L-ascorbate (TVL), or for 5 h in BHI supplemented with 7.4 mM sodium L-ascorbate. Compared to ∆ptxA, in WT S. mutans and CptxA, C10-KKWW had a stronger MIC (3.9 μg/mL), and distinctively decreased biofilm viability. The extracellular concentrations of L-ascorbate/sodium L-ascorbate were not changed before and after WT treated with C10-KKWW. L-ascorbate-induced operon genes, or other PTS genes, were significantly suppressed by C10-KKWW. In conclusion, C10-KKWW has been developed; it acts through interaction with the bacterial membrane and interferes with L-ascorbate translocation to inhibit S. mutans growth and eradicate its biofilm. C10-KKWW may be especially effective at optimal oral ascorbate levels. A combination of C10-KKWW with sodium L-ascorbate might also be a novel strategy for dental caries treatment.

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Antimicrobial and anti-biofilm effect of Bac8c on major bacteria associated with dental caries and Streptococcus mutans biofilms

Cited by 69 publications

References 30 publications

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Activity of Synthetic Antimicrobial Peptide GH12 against Oral Streptococci

A Membrane-Targeted Peptide Inhibiting PtxA of Phosphotransferase System Blocks <b><i>Streptococcus mutans</i></b>

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