scholarly journals Antimicrobial Peptide GH12 Prevents Dental Caries by Regulating Dental Plaque Microbiota

2020 ◽  
Vol 86 (14) ◽  
Author(s):  
Wentao Jiang ◽  
Yufei Wang ◽  
Junyuan Luo ◽  
Xiangshu Chen ◽  
Yuhao Zeng ◽  
...  
Keyword(s):  
Dental Caries ◽  
Antimicrobial Peptide ◽  
Microbial Ecology ◽  
Dental Plaque ◽  
Lactic Acid Production ◽  
Associated Bacteria ◽  
Caries Model ◽  
Multispecies Biofilms

ABSTRACT Due to the complex microecology and microenvironment of dental plaque, novel caries prevention strategies require modulating the microbial communities ecologically and reducing the cariogenic properties effectively. Antimicrobial peptide GH12 reduced the lactic acid production and exopolysaccharide (EPS) synthesis of a Streptococcus mutans biofilm and a three-species biofilm in vitro in previous studies. However, the anticaries effects and microecological effects of GH12 remained to be investigated in a complex biofilm model in vitro and an animal caries model in vivo. In the present study, GH12 at 64 mg/liter showed the most effective inhibition of lactic acid production, EPS synthesis, pH decline, and biofilm integrity of human dental plaque-derived multispecies biofilms in vitro, and GH12 at 64 mg/liter was therefore chosen for use in subsequent in vitro and in vivo assays. When treated with 64-mg/liter GH12, the dental plaque-derived multispecies biofilms sampled from healthy volunteers maintained its microbial diversity and showed a microbial community structure similar to that of the control group. In the rat caries model with a caries-promoting diet, 64-mg/liter GH12 regulated the microbiota of dental plaque, in which the abundance of caries-associated bacteria was decreased and the abundance of commensal bacteria was increased. In addition, 64-mg/liter GH12 significantly reduced the caries scores of sulcal and smooth surface caries in all locations. In conclusion, GH12 inhibited the cariogenic properties of dental plaque without perturbing the dental plaque microbiota of healthy individuals and GH12 regulated the dysbiotic microbial ecology and arrested caries development under cariogenic conditions. IMPORTANCE The anticaries effects and microecological regulation effects of the antimicrobial peptide GH12 were evaluated systematically in vitro and in vivo. GH12 inhibited the cariogenic virulence of dental plaque without overintervening in the microbial ecology of healthy individuals in vitro. GH12 regulated the microbial ecology of dental plaque to a certain extent in vivo under cariogenic conditions, increased the proportion of commensal bacteria, and decreased the abundance of caries-associated bacteria. GH12 significantly suppressed the incidence and severity of dental caries in vivo. This study thus describes an alternative antimicrobial therapy for dental caries.

scholarly journals A Novel Dental Caries Model Replacing, Refining, and Reducing Animal Sacrifice

2021 ◽  
Vol 11 (15) ◽  
pp. 7141
Author(s):  
Amit Wolfoviz-Zilberman ◽  
Yael Houri-Haddad ◽  
Nurit Beyth
Keyword(s):  
Dental Caries ◽  
Bacterial Growth ◽  
Control Group ◽  
In Vivo Models ◽  
Animal Sacrifice ◽  
Female Mice ◽  
Photographic Analysis ◽  
Caries Model

In vitro and in vivo models simulating the dental caries process enable the evaluation of anti-caries modalities for prevention and treatment. Animal experimentation remains important for improving human and animal health. Nonetheless, reducing animal sacrifice for research is desirable. The aim of the study was to establish a new reproducible in vitro caries model system and compare it to an in vivo model using similar conditions. Hemi-mandibles were extracted from previously euthanized healthy 10-week-old BALB/C female mice. Jaws were subjected to saliva, high-sucrose diet, and dental caries bacteria Streptococcus mutans UA159 for 5 days. Similar caries induction protocol was used in vivo in fifteen BALB/c female mice (6–7 weeks old) and compared to the in vitro model. Caries lesions were assessed clinically by photographic analysis and µCT analysis, and bacterial growth was evaluated. Under in vitro experimental conditions, carious lesions evolved within 5 days, prominently in the depth of the occlusal fissures in the control group as depicted by photographic analysis, µCT analysis, and bacterial growth. The developed in vitro caries model presented in this study may be a novel animal sparing model for caries disease studies and can be used widely to evaluate the efficacy of different antibacterial dental materials.

scholarly journals Dietary Nitrite Drives Disease Outcomes in Oral Polymicrobial Infections

2019 ◽  
Vol 98 (9) ◽  
pp. 1020-1026 ◽  
Author(s):  
J. Scoffield ◽  
S. Michalek ◽  
G. Harber ◽  
P. Eipers ◽  
C. Morrow ◽  
...  
Keyword(s):  
Dental Caries ◽  
Biofilm Formation ◽  
Reactive Nitrogen Species ◽  
Nitrosative Stress ◽  
Disease Outcomes ◽  
Carious Lesions ◽  
Caries Model ◽  
Polymicrobial Infections

Streptococcus mutans resides in the oral polymicrobial biofilm and is a major contributor to the development of dental caries. Interestingly, high salivary nitrite concentrations have been associated with a decreased prevalence of dental caries. Moreover, the combination of hydrogen peroxide–producing oral commensal streptococci and nitrite has been shown to mediate the generation of reactive nitrogen species, which have antimicrobial activity. The goal of this study was to examine whether nitrite affects S. mutans virulence during polymicrobial infections with the commensal Streptococcus parasanguinis. Here, we report that the combination of S. parasanguinis and nitrite inhibited S. mutans growth and biofilm formation in vitro. Glucan production, which is critical for S. mutans biofilm formation, was also inhibited in 2-species biofilms with S. parasanguinis containing nitrite as compared with biofilms that contained no nitrite. In the in vivo caries model, enamel and dentin carious lesions were significantly reduced in rats that were colonized with S. parasanguinis prior to infection with S. mutans and received nitrite in the drinking water, as compared with animals that had a single S. mutans infection or were co-colonized with both bacteria and received no nitrite. Last, we report that S. mutans LiaS, a sensor kinase of the LiaFSR 3-component system, mediates resistance to nitrosative stress. In summary, our data demonstrate that commensal streptococci and nitrite provide protection against S. mutans pathogenesis. Modulating nitrite concentrations in the oral cavity could be a useful strategy to combat the prevalence of dental caries.

scholarly journals A Multispecies Biofilm In Vitro Screening Model of Dental Caries for High-Throughput Susceptibility Testing

2019 ◽  
Vol 8 (2) ◽  
pp. 14 ◽  
Author(s):  
Lara A. Heersema ◽  
Hugh D. C. Smyth
Keyword(s):  
Dental Caries ◽  
High Throughput ◽  
High Throughput Screening ◽  
Kinetic Studies ◽  
Microtiter Plate ◽  
Multispecies Biofilm ◽  
Caries Model ◽  
Multispecies Model ◽  
Multispecies Biofilms

There is a current need to develop and optimize new therapeutics for the treatment of dental caries, but these efforts are limited by the relatively low throughput of relevant in vitro models. The aim of this work was to bridge the 96-well microtiter plate system with a relevant multispecies dental caries model that could be reproducibly grown to allow for the high-throughput screening of anti-biofilm therapies. Various media and inoculum concentrations were assessed using metabolic activity, biomass, viability, and acidity assays to determine the optimal laboratory-controlled conditions for a multispecies biofilm composed of Streptococcus gordonii, Streptococcus mutans, and Candida albicans. The selected model encompasses several of the known fundamental characteristics of dental caries-associated biofilms. The 1:1 RPMI:TSBYE 0.6% media supported the viability and biomass production of mono- and multispecies biofilms best. Kinetic studies over 48 h in 1:1 RPMI:TSBYE 0.6% demonstrated a stable biofilm phase between 10 and 48 h for all mono- and multispecies biofilms. The 1:1:0.1 S. gordonii: S. mutans: C. albicans multispecies biofilm in 1:1 RPMI:TSBYE 0.6% is an excellent choice for a high-throughput multispecies model of dental caries. This high-throughput multispecies model can be used for screening novel therapies and for better understanding the treatment effects on biofilm interactions and stability.

scholarly journals Core Microbiota Promotes the Development of Dental Caries

2021 ◽  
Vol 11 (8) ◽  
pp. 3638
Author(s):  
Jing Chen ◽  
Lixin Kong ◽  
Xian Peng ◽  
Yanyan Chen ◽  
Biao Ren ◽  
...  
Keyword(s):  
Dental Caries ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Core Microbiota ◽  
The Core ◽  
Enamel Demineralization ◽  
Caries Model

A previous longitudinal study about using microbiome as a caries indicator has successfully predicted early childhood caries (ECC) in healthy individuals, but there is no evidence to verify the composition of core microbiota and its pathogenicity in vitro and in vivo. Biofilm acidogenicity, S. mutans count, and biofilm composition were estimated by pH evaluation, colony-forming unit, and quantitative PCR, respectively. Extracellular polysaccharide production and enamel demineralization were observed by confocal laser scanning microscopy (CLSM) and transverse microradiography (TMR), respectively. A rat caries model was established for dental caries formation in vivo, and caries lesions were quantified by Keyes Scoring. We put forward that microbiota including Veillonella parvula, Fusobacterium nucleatum, Prevotella denticola, and Leptotrichia wadei served as the predictors for ECC may be the core microbiota in ECC. This study found that the core microbiota of ECC produced limited acid, but promoted growth and acidogenic ability of S. mutans. Besides, core microbiota could help to promote the development of biofilms. Moreover, the core microbiota enhanced the enamel demineralization in vitro and increased cariogenic potential in vivo. These results proved that core microbiota could promote the development of dental caries and plays an important role in the development of ECC.

scholarly journals Novel lactotransferrin-derived synthetic peptides suppress cariogenic bacteria in vitro and arrest dental caries in vivo

2021 ◽  
Vol 13 (1) ◽  
pp. 1943999
Author(s):  
Junyuan Luo ◽  
Zening Feng ◽  
Wentao Jiang ◽  
Xuelian Jiang ◽  
Yue Chen ◽  
...  
Keyword(s):  
Dental Caries ◽  
Synthetic Peptides ◽  
Cariogenic Bacteria

scholarly journals Bacteriocin-like activity of oral Fusobacterium nucleatum isolated from human and non-human primates

1999 ◽  
Vol 30 (4) ◽  
pp. 324-346 ◽  
Author(s):  
Elerson Gaetti-Jardim Júnior ◽  
Mario Julio Avila-Campos
Keyword(s):  
Oral Cavity ◽  
Microbial Ecology ◽  
Dental Plaque ◽  
Fusobacterium Nucleatum ◽  
Antagonistic Activity ◽  
Healthy Individuals ◽  
Bacterial Microbiota ◽  
Reference Strains

Fusobacterium nucleatum is indigenous of the human oral cavity and has been involved in different infectious processes. The production of bacteriocin-like substances may be important in regulation of bacterial microbiota in oral cavity. The ability to produce bacteriocin-like substances by 80 oral F. nucleatum isolates obtained from periodontal patients, healthy individuals and Cebus apella monkeys, was examinated. 17.5% of all tested isolates showed auto-antagonism and 78.8% iso- or hetero-antagonism. No isolate from monkey was capable to produce auto-inhibition. In this study, the antagonistic substances production was variable in all tested isolates. Most of the F. nucleatum showed antagonistic activity against tested reference strains. These data suggest a possible participation of these substances on the oral microbial ecology in humans and animals. However, the role of bacteriocins in regulating dental plaque microbiota in vivo is discussed.

scholarly journals The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

2018 ◽  
Vol 51 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Bobin Mi ◽  
Jing Liu ◽  
Yi Liu ◽  
Liangcong Hu ◽  
Yukun Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Structural Stability ◽  
Cell Counting ◽  
Sprague Dawley ◽  
Skin Wound Healing ◽  
High Sodium

Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca2+ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

scholarly journals Intraoral Fluoride-Releasing Devices: A Literature Review

2012 ◽  
Vol 3 (4) ◽  
pp. 350-354 ◽  
Author(s):  
Jagjit Singh ◽  
Gurminder Singh ◽  
Ramandeep Singh Gambhir ◽  
Daljit Kapoor ◽  
Heena Kakar
Keyword(s):  
Dental Caries ◽  
Literature Review ◽  
Fluoride Concentration ◽  
Risk Groups ◽  
High Caries Risk ◽  
Release Devices ◽  
Topical Fluorides

ABSTRACT Dental caries still continues to be a problem for majority of the individuals and it can be a serious problem for medically compromised, developmentally disabled and elderly individuals. Water fluoridation, systemic and topical fluorides are used for past many years to supply supplemental fluoride in order to combat dental caries. The latest fluoride research is investigating the use of slow-release devices for the long-term intraoral provision of fluoride. The present review addresses two main types of intraoral fluoride-releasing devices like the copolymer membrane device, glass device containing fluoride and some variations of these devices. These devices can significantly increase the salivary fluoride concentration without substantially affecting the urinary fluoride levels. A significant number of studies have confirmed that intraoral fluoride-releasing devices have great potential for use in preventing dental caries in children, high-caries-risk groups, and irregular dental attenders in addition to a number of other applications. As most of the studies done on these devices are in vitro and in vivo studies, more well-designed clinical trials are necessary to evaluate the results so that these devices can be used clinically. How to cite this article Gambhir RS, Kapoor D, Singh G, Singh J, Kakar H. Intraoral Fluoride-Releasing Devices: A Literature Review. World J Dent 2012;3(4):350-354.

scholarly journals Antitumor Activity and Mechanism of Action of the Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide

2021 ◽  
Author(s):  
Mickael COUTY ◽  
Marie DUSAUD ◽  
Mickael MIRO-PADOVANI ◽  
Liuhui ZHANG ◽  
Patricia ZADIGUE ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antimicrobial Peptide ◽  
Tumor Cell Line ◽  
Experimental Approaches ◽  
Prostate Cancers ◽  
Innovative Drugs ◽  
Therapeutic Alternatives ◽  
Prostate Tumor Cells

Abstract Prostate cancer represents the most common cancer in men. For patients with advanced or metastatic form, treatments will be able to slow down the progression but cannot cure it even with the used of new targeted therapies. In this context, the development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2 (DRS-B2), a natural multifunctional antimicrobial peptide isolated from the Amazonian frog skin, has been reported to possess antitumor and antiangiogenic activities. To improve DRS-B2 pharmacological properties and target prostate tumor cells more specifically, we have developed a chimeric molecule, called Hormonotoxin (H-B2) which is composed of a DRS-B2 combined with a hormonal analog, d-Lys6-LHRH, to target LHRH-Receptor which is overexpressed in more than 85% of prostate cancers. In vitro H-B2 has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of DRS-B2. The antitumor activity of H-B2 was confirmed in vivo in mouse model xenografted with PC3 tumors and appears to be better tolerated than DRS-B2. Biophysical experiments showed that the addition of the hormonal analog to DRS-B2 did not alter either its secondary structure or its biological activity. Combination of different experimental approaches indicated that H-B2 induces cell death by an apoptotic mechanism whereas DRS-B2 was shown to induce it by necrosis. These results could explain the H-B2 less toxicity compared to DRS-B2. H-B2 represents a promising targeting approach for cancer therapy.

Antibacterial Activity and Anti-Biofilm Effect of Chitosan against Strains of Streptococcus Mutans Isolated in Dental Plaque

2008 ◽  
Vol 21 (4) ◽  
pp. 993-997 ◽  
Author(s):  
G. Pasquantonio ◽  
C. Greco ◽  
M. Prenna ◽  
C. Ripa ◽  
L.A. Vitali ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Streptococcus Mutans ◽  
Dental Plaque ◽  
Chitosan Solution ◽  
Positive Control ◽  
Phases Of Development ◽  
Adhesion Phase ◽  
Adult Volunteers

Streptococcus mutans is the major cause of dental plaque and is often associated with biofilm formation. The aim of this study is to evaluate the activity of a hydrosoluble derivative of chitosan against S. mutans biofilms in vitro and in vivo. Strains of S. mutans were isolated from the dental plaque of 84 patients enrolled in the study. The antibacterial activity of chitosan was determined by broth microdilutions. The effect of chitosan at different concentrations and exposure times on S. mutans biofilms at different phases of development was assessed by a clinical study using the classical “4-day plaque regrowth” experiment in adult volunteers. The MIC values of chitosan were between 0.5 and 2 g/L. Compared to distilled water, the chitosan solution significantly decreased the vitality of plaque microflora (p≤0.05). Chlorhexidine, used as a positive control, reduced vitality even further. The results showed that S. mutans in the adhesion phase (4 h) was completely inhibited by chitosan at any concentration (0.1, 0.2, 0.5XMIC) or exposure time investigated (1, 15, 30, 60 min), while S. mutans at successive stages of accumulation (12–24 h) was inhibited only by higher concentrations and longer exposure times. These data confirm the effective action of chitosan against S. mutans biofilms.

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