scholarly journals Synthetic antigen-binding fragments (Fabs) against S. mutans and S. sobrinus inhibit caries formation

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Md. Kausar Alam ◽  
Li Zheng ◽  
Ruirui Liu ◽  
Silvana Papagerakis ◽  
Petros Papagerakis ◽  
...  
Keyword(s):  
Dental Caries ◽  
Biofilm Formation ◽  
Passive Immunization ◽  
Tooth Surface ◽  
Antigen Binding ◽  
Streptococcus Sobrinus ◽  
Immunization Strategies ◽  
Caries Model ◽  
Causative Agents

Abstract Streptococcus mutans and Streptococcus sobrinus are the main causative agents of human dental caries. Current strategies for treating caries are costly and do not completely eradicate them completely. Passive immunization using nonhuman antibodies against Streptococcal surface antigens has shown success in human trials, however they often invoke immune reactions. We used phage display to generate human antigen-binding fragments (Fabs) against S. mutans and S. sobrinus. These Fabs were readily expressed in E. coli and bound to the surface S. mutans and S. sobrinus. Fabs inhibited sucrose-induced S. mutans and S. sobrinus biofilm formation in vitro and a combination of S. mutans and S. sobrinus Fabs prevented dental caries formation in a rat caries model. These results demonstrated that S. mutans and S. sobrinus Fabs could be used in passive immunization strategies to prevent dental caries. In the future, this strategy may be applied towards a caries therapy, whereby Fabs are topically applied to the tooth surface.

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 CHEWING GUM CONTAINING PROPOLIS WAX FROM APIS MELLIFERA BEES FOR PREVENTION OF DENTAL CARIES DISEASE

2019 ◽  
pp. 141-145
Author(s):  
SRI ANGKY SOEKANTO ◽  
ASTRID LEVINA ◽  
EKA NURIN SHARFINA IRIANTO ◽  
ACHMAD HUDA FAUZI ADZIMA ◽  
HERI HERMANSYAH ◽  
...  
Keyword(s):  
Dental Caries ◽  
Biofilm Formation ◽  
Antibacterial Properties ◽  
Salivary Flow ◽  
Disease Stage ◽  
Tooth Surface ◽  
Chewing Gum ◽  
Scanning Calorimetry ◽  
Negative Controls

Objective: Dental caries is caused by demineralization of the tooth surface by organic acids as a result of metabolism of cariogenic bacteria, especiallyStreptococcus mutans. Chewing gum has been proven to help prevent dental caries formation by stimulating salivary flow and thus reducing theavailability of nutrients for cariogenic bacteria.Methods: In this study, sugar-free chewing gum was formulated using latex from the jelutong tree (Dyera costuata) with the addition of propolis wax(1–5%) as an antibacterial agent to inhibit the activity of S. mutans and prevent biofilm formation, which is an early disease stage of dental caries.Characterization of jelutong latex using differential scanning calorimetry and thermogravimetric analysis shows that the latex has glass transitiontemperatures of −22.46°C and 33.86°C, and it contains volatile (14.96%), polymer (84.43%), organic (0.36%), and inorganic (0.25%) components.The propolis wax used in this formulation mostly contains resin and wax and is a purification by-product of raw propolis obtained from Apis mellifera.Results: Flavonoids acting as antibacterial compounds are found in propolis, and presumably are also found in propolis wax; thus, probably thiscompound also has the antibacterial properties of propolis. The in vitro testing showed that 5% propolis wax in sugar-free chewing gum can preventthe formation of dental caries by inhibiting biofilm formation with up to 80% more effectiveness relative to negative controls (without chewing gum).Conclusion: Propolis wax chewing gum can inhibit the formation of dental caries disease.

Polydimethylsiloxane as a Tooth Surface-Bound Carrier of Triclosan: a New Concept in Chemical Plaque Inhibition

1994 ◽  
Vol 8 (2) ◽  
pp. 272-277 ◽  
Author(s):  
G. Rølla ◽  
J.E. Ellingsen ◽  
D. Gaare
Keyword(s):  
Silicone Oil ◽  
Dental Enamel ◽  
Solid Surfaces ◽  
Tooth Surface ◽  
Water Repellent ◽  
Streptococcus Sobrinus ◽  
Gingival Health ◽  
Low Solubility

Polydimethylsiloxane (silicone oil) has an extremely low surface tension: It spreads over solid surfaces and forms a tenacious film which is hydrophobic and water-repellent. It is known that this liquid binds to hydroxyapatite and to dental enamel and changes the properties of these solids. It has been suggested that silicone oil may be applied to teeth and serve as a reservoir of lipid-soluble antibacterial substances which presumably will be slowly released into saliva due to their low solubility in water. The present paper reviews recent papers where this hypothesis is tested in vitro and in vivo. It was first shown that test tubes treated with the combination silicone oil and the lipid-soluble agent triclosan acquired a layer which inhibited bacterial growth in a culture of Streptococcus sobrinus (OMZ 176) which was grown in sucrose. Both growth in the medium and polysaccharide adsorption to the glass wall were inhibited. Silicone oil alone inhibited polysaccharide adsorption to some degree, whereas the growth in the medium was not affected. In a similar clinical plaque-inhibition study, topical application of silicone oil/triclosan to the teeth of a test panel showed marked plaque inhibition, particularly giving an increased number of teeth with scores of 0 (no plaque). In a study where silicone oil and triclosan were incorporated into a toothpaste, improved gingival health was observed after a period of one month. It is concluded that the use of silicone oil/ triclosan in the manner described above represents a new principle in preventive dentistry. The results obtained seem to warrant further experiments with this combination.

scholarly journals Expression of biofilm-associated genes of Streptococcus mutans in response to glucose and sucrose

2007 ◽  
Vol 56 (11) ◽  
pp. 1528-1535 ◽  
Author(s):  
Moshe Shemesh ◽  
Avshalom Tam ◽  
Doron Steinberg
Keyword(s):  
Gene Expression ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Fold Increase ◽  
Extracellular Polysaccharide ◽  
Tooth Surface ◽  
Differential Analysis ◽  
Nutrient Contents ◽  
Genes Encoding

Streptococcus mutans is known as a primary pathogen of dental caries, one of the most common human infectious diseases. Exopolysaccharide synthesis, adherence to tooth surface and biofilm formation are important physiological and virulence factors of S. mutans. In vitro comparative gene expression analysis was carried out to differentiate 10 selected genes known to be mostly involved in S. mutans biofilm formation by comparing the expression under biofilm and planktonic environments. Real-time RT-PCR analyses indicated that all of the genes tested were upregulated in the biofilm compared to cells grown in planktonic conditions. The influence of simple dietary carbohydrates on gene expression in S. mutans biofilm was tested also. Among the tested genes, in the biofilm phase, the greatest induction was observed for gtf and ftf, which are genes encoding the extracellular polysaccharide-producing enzymes. Biofilm formation was accompanied by a 22-fold induction in the abundance of mRNA encoding glucosyltransferase B (GTFB) and a 14.8 -fold increase in mRNA encoding GTFC. Levels of mRNA encoding fructosyltransferase were induced approximately 11.8-fold in biofilm-derived cells. Another notable finding of this study suggests that glucose affects the expression of S. mutans GS5 biofilm genes. In spite of a significant upregulation in biofilm-associated gene expression in the presence of sucrose, the presence of glucose with sucrose reduced expression of most tested genes. Differential analysis of the transcripts from S. mutans, grown in media with various nutrient contents, revealed significant shifts in the expression of the genes involved in biofilm formation. The results presented here provide new insights at the molecular level regarding gene expression in this bacterium when grown under biofilm conditions, allowing a better understanding of the mechanism of biofilm formation by S. mutans.

scholarly journals Murein Hydrolase LytF of Streptococcus sanguinis and the Ecological Consequences of Competence Development

2017 ◽  
Vol 83 (24) ◽  
Author(s):  
Nyssa Cullin ◽  
Sylvio Redanz ◽  
Kirsten J. Lampi ◽  
Justin Merritt ◽  
Jens Kreth
Keyword(s):  
Dental Caries ◽  
Oral Cavity ◽  
Cell Morphology ◽  
Biofilm Formation ◽  
Oral Bacteria ◽  
Tooth Surface ◽  
Content Type ◽  
Streptococcus Sanguinis ◽  
Murein Hydrolase ◽  
Biofilm Development

ABSTRACT The overall health of the oral cavity is dependent on proper homeostasis between health-associated bacterial colonizers and bacteria known to promote dental caries. Streptococcus sanguinis is a health-associated commensal organism, a known early colonizer of the acquired tooth pellicle, and is naturally competent. We have shown that LytF, a competence-controlled murein hydrolase, is capable of inducing the release of extracellular DNA (eDNA) from oral bacteria. Precipitated LytF and purified LytF were used as treatments against planktonic cultures and biofilms. Larger amounts of eDNA were released from cultures treated with protein samples containing LytF. Additionally, LytF could affect biofilm formation and cellular morphology. Biofilm formation was significantly decreased in the lytF-complemented strain, in which increased amounts of LytF are present. The same strain also exhibited cell morphology defects in both planktonic cultures and biofilms. Furthermore, the LytF cell morphology phenotype was reproducible in wild-type cells using purified LytF protein. In sum, our findings demonstrate that LytF can induce the release of eDNA from oral bacteria, and they suggest that, without proper regulation of LytF, cells display morphological abnormalities that contribute to biofilm malformation. In the context of the oral biofilm, LytF may play important roles as part of the competence and biofilm development programs, as well as increasing the availability of eDNA. IMPORTANCE Streptococcus sanguinis, a commensal organism in the oral cavity and one of the pioneer colonizers of the tooth surface, is associated with the overall health of the oral environment. Our laboratory showed previously that, under aerobic conditions, S. sanguinis can produce H2O2 to inhibit the growth of bacterial species that promote dental caries. This production of H2O2 by S. sanguinis also induces the release of eDNA, which is essential for proper biofilm formation. Under anaerobic conditions, S. sanguinis does not produce H2O2 but DNA is still released. Determining how S. sanguinis releases DNA is thus essential to understand biofilm formation in the oral cavity.

scholarly journals Spatial Arrangements and Associative Behavior of Species in an In Vitro Oral Biofilm Model

2001 ◽  
Vol 67 (3) ◽  
pp. 1343-1350 ◽  
Author(s):  
M. Guggenheim ◽  
S. Shapiro ◽  
R. Gmür ◽  
B. Guggenheim
Keyword(s):  
Biofilm Formation ◽  
Laser Scanning ◽  
Fusobacterium Nucleatum ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Streptococcus Sobrinus ◽  
Growth Phenomenon ◽  
Associative Behavior ◽  
Species Specific

ABSTRACT The spatial arrangements and associative behavior ofActinomyces naeslundii, Veillonella dispar, Fusobacterium nucleatum, Streptococcus sobrinus, and Streptococcus oralis strains in an in vitro model of supragingival plaque were determined. Using species-specific fluorescence-labeled antibodies in conjunction with confocal laser scanning microscopy, the volumes and distribution of the five strains were assessed during biofilm formation. The volume-derived cell numbers of each strain correlated well with respective culture data. Between 15 min and 64 h, populations of each strain increased in a manner reminiscent of batch growth. The microcolony morphologies of all members of the consortium and their distributions within the biofilm were characterized, as were interspecies associations. Biofilms formed 15 min after inoculation consisted principally of single nonaggregated cells. All five strains adhered strongly to the saliva-conditioned substratum, and therefore, coadhesion played no role during the initial phase of biofilm formation. This observation does not reflect the results of in vitro coaggregation of the five strains, which depended upon the nature of the suspension medium. While the possibility cannot be excluded that some interspecies associations observed at later stages of biofilm formation were initiated by coadhesion, increase in bacterial numbers appeared to be largely a growth phenomenon regulated by the prevailing cultivation conditions.

scholarly journals Salivary Mucins Protect Surfaces from Colonization by Cariogenic Bacteria

2014 ◽  
Vol 81 (1) ◽  
pp. 332-338 ◽  
Author(s):  
Erica Shapiro Frenkel ◽  
Katharina Ribbeck
Keyword(s):  
Dental Caries ◽  
Biofilm Formation ◽  
Defense Mechanism ◽  
Tooth Enamel ◽  
Tooth Surface ◽  
Oral Diseases ◽  
Surface Attachment ◽  
Content Type ◽  
Treatment And Prevention ◽  
Planktonic Form

ABSTRACTUnderstanding how the body's natural defenses function to protect the oral cavity from the myriad of bacteria that colonize its surfaces is an ongoing topic of research that can lead to breakthroughs in treatment and prevention. One key defense mechanism on all moist epithelial linings, such as the mouth, gastrointestinal tract, and lungs, is a layer of thick, well-hydrated mucus. The main gel-forming components of mucus are mucins, large glycoproteins that play a key role in host defense. This study focuses on elucidating the connection between MUC5B salivary mucins and dental caries, one of the most common oral diseases. Dental caries is predominantly caused byStreptococcus mutansattachment and biofilm formation on the tooth surface. OnceS. mutansattaches to the tooth, it produces organic acids as metabolic by-products that dissolve tooth enamel, leading to cavity formation. We utilize CFU counts and fluorescence microscopy to quantitatively show thatS. mutansattachment and biofilm formation are most robust in the presence of sucrose and that aqueous solutions of purified human MUC5B protect surfaces by acting as an antibiofouling agent in the presence of sucrose. In addition, we find that MUC5B does not alterS. mutansgrowth and decreases surface attachment and biofilm formation by maintainingS. mutansin the planktonic form. These insights point to the importance of salivary mucins in oral health and lead to a better understanding of how MUC5B could play a role in cavity prevention or diagnosis.

scholarly journals Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

2020 ◽  
Vol 6 (6) ◽  
pp. eaay9258 ◽  
Author(s):  
Annalee W. Nguyen ◽  
Andrea M. DiVenere ◽  
James F. Papin ◽  
Sheila Connelly ◽  
Michael Kaleko ◽  
...  
Keyword(s):  
Infant Mortality ◽  
Pertussis Toxin ◽  
World Wide ◽  
Clinical Symptoms ◽  
Passive Immunization ◽  
Immunization Strategies ◽  
Baboon Model ◽  
Established Disease ◽  
Antibody Cocktail

Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.

Role of sweeteners in the etiology and prevention of dental caries

2002 ◽  
Vol 74 (7) ◽  
pp. 1293-1300 ◽  
Author(s):  
Shigeyuki Hamada
Keyword(s):  
Dental Caries ◽  
Mutans Streptococci ◽  
Tooth Surface ◽  
Surface Attachment ◽  
Epidemiological Surveys ◽  
High Prevalence ◽  
Insoluble Glucan ◽  
Causative Agents ◽  
Glucan Synthesis ◽  
Major Factors

Dental caries is a multifactorial disease that is caused by an interplay of three major factors, i.e., teeth, cariogenic bacteria, and fermentable sugars. Streptococcus mutans and S. sobrinus, collectively termed mutans streptococci (MS), are principal causative agents of dental caries. Initial MS-tooth surface attachment is followed by firm and irreversible adhesion of MS to the tooth surface, accompanied by the synthesis of water-insoluble glucan from sucrose via enzymatic action of glucosyltransferases (GTases). MS induce severe dental caries in rats fed on a high-sucrose diet. Epidemiological surveys indicate that frequent sucrose intakes are associated with high prevalence of dental caries in humans. In contrast, dietary sucrose restrictions and/or use of nonfermentable sucrose substitutes clearly influence the GTase activities of MS, resulting in decreased caries development. Structural isomers of sucrose (i.e., disaccharides composed of glucose and fructose with different linkages) will not function as substrates for GTases of MS, nor be utilized as energy sources by MS. Palatinose and trehalulose are included in this category, and are produced in commercial scales in Japan. Glucose oligomers containing α-1, 6 and/or α-1, 4 linkages are found to inhibit glucan synthesis by MS from sucrose, although these oligomers are hydrolyzed by MS to release acids. Lastly, sugar alcohols, including maltitol and palatinit, are useful as noncaries-inducing sweeteners.

scholarly journals Anti-biofilm activities of a novel chimeolysin againstS. mutansin physiological and cariogenic conditions

2016 ◽  
pp. AAC.01872-16 ◽  
Author(s):  
Hang Yang ◽  
Yongli Bi ◽  
Xiaoran Shang ◽  
Mengyue Wang ◽  
Sara B. Linden ◽  
...  
Keyword(s):  
Dental Caries ◽  
Treated Group ◽  
Tooth Surface ◽  
Log Reduction ◽  
Colonization Model ◽  
Group A ◽  
Repeated Use ◽  
Susceptibility Tests

Streptococcus mutansoften survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, againstS. mutansbiofilms in physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinicalS. mutansisolates tested as well asS. mutansbiofilms that displayed resistance to penicillin.S. mutansbiofilms formed on hydroxyapatite discs in physiological sugar conditions and cariogenic conditions were reduced ∼2 logs and 3 logs after treatment with 100 μg/ml ClyR, respectively. In comparison, only 1 log reduction was observed in the chlorhexidine (ChX) treated group, and no killing effect was observed in the NaF treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 μg/day) reduced the number of colonizedS. mutansin the dental plaques significantly (p<0.05), without harmful effects on mice. Furthermore, toxicity was not noted at concentrations exceeding those used for these studies and ClyR-specific antibodies could not be detected in mice saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrates that ClyR is active againstS. mutansbiofilms bothin vitroandin vivo, thus representing a preventative or therapeutic agent against dental caries.

Sign in / Sign up

Export Citation Format

Share Document