scholarly journals In silico Identification of Potential Inhibitor Targeting Streptococcus mutans and Lactobacillus Acidophilus for the Treatment of Dental Caries

2021 ◽  
pp. 148-160
Author(s):  
M. Chittrarasu ◽  
A. Shafie Ahamed ◽  
A. Andamuthu Sivakumar
Keyword(s):  
Binding Energy ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Ellagic Acid ◽  
Lactobacillus Acidophilus ◽  
Surface Proteins ◽  
Tooth Surface ◽  
Protein Database ◽  
Potential Inhibitor ◽  
Alpha Glucosidase

Background: Dental caries is one of the most common chronic diseases, and it is caused by the acid fermentation of bacteria that have become attached to the teeth. Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus) anchor surface proteins to the cell wall and form a biofilm to aid adhesion to the tooth surface. Some natural plant products, particularly several flavonoids, are effective inhibitors. However, given the scarcity of inhibitors and the emergence of drug resistance, the development of new inhibitors is critical. The high-throughput virtual screening approach was used in this study to identify new potential inhibitor of against S. mutans and L. acidophilus by using ligand (Ellagic acid). Aim: To evaluate the drug interaction ligand (Ellagic acid) and protein [A3VP1 of AgI/II] of Streptococcus mutans (PDB ID: 3IPK), glucan-1,6 - alpha-glucosidase from Lactobacillus acidophilus NCFM (PDB ID: 4AIE). Materials and Methodology: The pdb format of two selected proteins was retrieved from the RCSB protein database. Then inhibitors were docked with protein (A3VP1 of AgI/II) and glucan-1,6-alpha-glucosidase to identify the potent inhibitor. An evaluation criterion was based on the binding affinities by using AutoDock. Results: The binding energy of Ellagic acid - Streptococcus mutans docked complex-10.63 kcal/mol and with Ellagic acid – Lactobacillus acidophilus docked complex was -7.30 kcal/mol. Conclusion: In this study, Showed that lesser binding energy better is the binding of the ligand and protein. These findings can provide a new strategy for dental caries disease therapy by using Ellagic acid as a inhibitor against  Streptococcus mutans and Lactobacillus acidophilus

scholarly journals Intranasal Immunization against Dental Caries with a Streptococcus mutans-Enriched Fimbrial Preparation

1999 ◽  
Vol 6 (3) ◽  
pp. 405-409 ◽  
Author(s):  
Margherita Fontana ◽  
Ann J. Dunipace ◽  
George K. Stookey ◽  
Richard L. Gregory
Keyword(s):  
Dental Caries ◽  
Cholera Toxin ◽  
Streptococcus Mutans ◽  
Surface Proteins ◽  
Mucosal Vaccine ◽  
Tooth Surface ◽  
Cholera Toxin B Subunit ◽  
Sprague Dawley ◽  
Igg Antibody ◽  
Group A

ABSTRACT Streptococcus mutans has been identified as the major etiological agent of human dental caries. The first step in the initiation of infection by this pathogenic bacterium is its attachment (i.e., through bacterial surface proteins such as glucosyltransferases, P1, glucan-binding proteins, and fimbriae) to a suitable receptor. It is hypothesized that a mucosal vaccine against a combination ofS. mutans surface proteins would protect against dental caries by inducing specific salivary immunoglobulin A (IgA) antibodies which may reduce bacterial pathogenesis and adhesion to the tooth surface by affecting several adhesins simultaneously. Conventional Sprague-Dawley rats, infected withS. mutans at 18 to 20 days of age, were intranasally immunized with a mixture of S. mutans surface proteins, enriched for fimbriae and conjugated with cholera toxin B subunit (CTB) plus free cholera toxin (CT) at 13, 15, 22, 29, and 36 days of age (group A). Control rats were either not immunized (group B) or immunized with adjuvant alone (CTB and CT [group C]). At the termination of the study (when rats were 46 days of age), immunized animals (group A) had significantly (P < 0.05) higher salivary IgA and serum IgG antibody responses to the mixture of surface proteins and to whole bacterial cells than did the other two groups (B and C). No significant differences were found in the average numbers of recoveredS. mutans cells among groups. However, statistically fewer smooth-surface enamel lesions (buccal and lingual) were detected in the immunized group than in the two other groups. Therefore, a mixture of S. mutans surface proteins, enriched with fimbria components, appears to be a promising immunogen candidate for a mucosal vaccine against dental caries.

scholarly journals Essential Roles of thesppRAFructose-Phosphate Phosphohydrolase Operon in Carbohydrate Metabolism and Virulence Expression byStreptococcus mutans

2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Lin Zeng ◽  
Robert A. Burne
Keyword(s):  
Dental Caries ◽  
Organic Acids ◽  
Streptococcus Mutans ◽  
Biochemical Characterization ◽  
Constitutive Expression ◽  
Extracellular Dna ◽  
Tooth Surface ◽  
Oral Diseases ◽  
Sugar Phosphate ◽  
Content Type

ABSTRACTThe dental caries pathogenStreptococcus mutanscan ferment a variety of sugars to produce organic acids. Exposure ofS. mutansto certain nonmetabolizable carbohydrates, such as xylitol, impairs growth and can cause cell death. Recently, the presence of a sugar-phosphate stress inS. mutanswas demonstrated using a mutant lacking 1-phosphofructokinase (FruK) that accumulates fructose-1-phosphate (F-1-P). Here, we studied an operon inS. mutans,sppRA, which was highly expressed in thefruKmutant. Biochemical characterization of a recombinant SppA protein indicated that it possessed hexose-phosphate phosphohydrolase activity, with preferences for F-1-P and, to a lesser degree, fructose-6-phosphate (F-6-P). SppA activity was stimulated by Mg2+and Mn2+but inhibited by NaF. SppR, a DeoR family regulator, repressed the expression of thesppRAoperon to minimum levels in the absence of the fructose-derived metabolite F-1-P and likely also F-6-P. The accumulation of F-1-P, as a result of growth on fructose, not only inducedsppAexpression, but it significantly altered biofilm maturation through increased cell lysis and enhanced extracellular DNA release. Constitutive expression ofsppA, via a plasmid or by deletingsppR, greatly alleviated fructose-induced stress in afruKmutant, enhanced resistance to xylitol, and reversed the effects of fructose on biofilm formation. Finally, by identifying three additional putative phosphatases that are capable of promoting sugar-phosphate tolerance, we show thatS. mutansis capable of mounting a sugar-phosphate stress response by modulating the levels of certain glycolytic intermediates, functions that are interconnected with the ability of the organism to manifest key virulence behaviors.IMPORTANCEStreptococcus mutansis a major etiologic agent for dental caries, primarily due to its ability to form biofilms on the tooth surface and to convert carbohydrates into organic acids. We have discovered a two-gene operon inS. mutansthat regulates fructose metabolism by controlling the levels of fructose-1-phosphate, a potential signaling compound that affects bacterial behaviors. With fructose becoming increasingly common and abundant in the human diet, we reveal the ways that fructose may alter bacterial development, stress tolerance, and microbial ecology in the oral cavity to promote oral diseases.

scholarly journals Antibiofilm Activity of Mangosteen (Garcinia mangostana L.) Flavonoids against Streptococcus mutans Bacteria

2020 ◽  
Vol 10 (2) ◽  
pp. 48
Author(s):  
Sri Kunarti ◽  
Aulia Ramadhani ◽  
Laskmiari Setyowati
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Tooth Enamel ◽  
Tooth Surface ◽  
Control Group ◽  
Antibiofilm Activity ◽  
Garcinia Mangostana ◽  
Control Group Design ◽  
Biofilm Inhibition ◽  
Significant Difference

Background: Dental caries is one of the most common infectious diseases and often occurs in the community caused by bacteria. Attached bacteria in the tooth surface for a long time will form a biofilm and will lead to demineralization characterized by damage in the structure of the tooth enamel. The bacteria that cause dental caries and can form biofilms is Streptococcus mutans. The bacteria inside biofilms are more resistant to antibacterial agents. Flavonoids in mangosteen pericarp extract can be a cleaner alternative for the anti-biofilm cavity that has properties against Streptococcus mutans. Purpose: To determine the activity of flavonoids in mangosteen pericarp extract at a certain concentration against Streptococcus mutans bacteria. Methods: This study was a laboratory experimental study with a post-test only control group design. Streptococcus mutans were diluted according to the Mc Farland dilution standard 106 in Tryptic Soy Broth (TSB) medium and put in a flexible U-bottom microtiter plate. Then it was incubated for 5x24 hours and checked using crystal violet simple staining to see the formation of biofilms. Flavonoid extract of mangosteen pericarp performed serial dilution in a concentration of 100%, 50%, 25%, 12.5%, 6.25%, 3.125%, 1.56%, and 0.78% was added, and the incubation process were conducted for 1x24 hours. OD (Optical Density) readings were done with a wavelength of 595 nm. Results: There was a significant difference between the test groups and the positive control group. The concentration of 100% had the anti-biofilm activity and showed the value of the highest percentage of inhibition, whilst the concentration of 0.78% showed a minimum biofilm inhibition concentration. The results were demonstrated by a statistical analysis test. Conclusion: Flavonoid extract of mangosteen pericarp at a certain concentration has anti-biofilm activity against Streptococcus mutans biofilm.

scholarly journals Effect of Prebiotics-Enhanced Probiotics on the Growth ofStreptococcus mutans

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Santichai Nunpan ◽  
Chatrudee Suwannachart ◽  
Kornchanok Wayakanon
Keyword(s):  
Growth Rate ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Lactobacillus Acidophilus ◽  
Digestive System ◽  
Acidic Environment ◽  
Beneficial Microorganisms ◽  
Carious Lesions ◽  
Significant Difference ◽  
Stimulation Of

Streptococcus mutanspredominantly creates an acidic environment in an oral cavity. This results in dental demineralization and carious lesions. The probiotics are beneficial microorganisms that modulate the bacterial balance in the digestive system. Prebiotics are defined as nondigestible oligosaccharides that are utilized for the selective stimulation of the beneficial microorganisms. The objective of this study was to evaluate the efficacy of the prebiotics, galactooligosaccharides (GOS) and fructooligosaccharides (FOS), for enhancing the probioticLactobacillus acidophilusATCC 4356, for inhibitingStreptococcus mutans(A32-2) for the prevention of dental caries. The growth rate of theS. mutanssignificantly decreased when cocultured withL. acidophilusin the GOS-supplemented medium at 3%, 4%, and 5%. In the FOS-supplemented medium, the growth rate ofS. mutanssignificantly decreased in all concentrations when cocultured withL. acidophilus. There was no significant difference in the growth rate ofL. acidophilusin all concentrations of either GOS or FOS. It can be concluded that the growth rate ofS. mutanswas significantly retarded when cocultured withL. acidophilusand the proper concentration of prebiotics. These prebiotics have potential for a clinical application to activate the function of the naturally intraoralL. acidophilusto inhibitS. mutans.

scholarly journals Cloning, Expression, Purification, and Preliminary Characterization of Single-Crystal X-Ray Diffraction of Glucosyltransferase B of Streptococcus mutans

2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1984933
Author(s):  
Joshua L. Mieher ◽  
Norbert Schormann ◽  
Manisha Patel ◽  
Hui Wu ◽  
Champion Deivanayagam
Keyword(s):  
Dental Caries ◽  
Oral Cavity ◽  
Single Crystal ◽  
Streptococcus Mutans ◽  
Tooth Enamel ◽  
Tooth Surface ◽  
X Ray Diffraction ◽  
Persistent Disease ◽  
X Ray

Dental caries characterized by acid damage of tooth enamel is a persistent disease that begins with the formation of biofilms on the tooth surface. The secreted glucosyltransferases enable Streptococcus mutans to synthesize extracellular glucan polymers using ingested starch within the oral cavity, which eventually results in the production of acid, a contributing factor to cariogenesis. In this paper, we report the cloning, expression, purification, crystallization, and preliminary X-ray diffraction characterization of glucosyltransferase B.

scholarly journals Uji Konsentrasi Hambat Minimum Ekstrak Daun Gedi (Abelmoschus manihot L.) terhadap Pertumbuhan Bakteri Streptococcus Mutans

e-GIGI ◽  
2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Helen N. Sekeon ◽  
Heriyannis Homenta ◽  
Michael A. Leman
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Leaf Extract ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Tooth Surface ◽  
Control Group ◽  
Control Group Design ◽  
Cariogenic Bacteria ◽  
Group Design

Abstract: Streptococcus mutans is the most common bacterium that causes dental caries due to its ability to ferment carbohydrates into acid resulting in the decreased pH on the tooth surface. Prevention of dental caries could be achieved by inhibiting the growth of cariogenic bacteria. Various efforts to control and prevent the cariogenic bacteria include the usage of herbal ingredients; one of them is gedi leaves (Abelmoschus manihot L.). These gedi leaves contain bioactive compounds such as flavonoids, alkaloids, steroids, and saponins. This study was aimed to prove that gedi leaf extract had inhibitory effect on the growth of S.mutans and to obtain the minimum inhibitory concentration (MIC) of this extract on the growth of S. mutans. This was a true experimental design with a randomized pretest-posttest control group design. Gedi leaf extract was obtained by maceration method in 96% ethanol. The results showed that gedi leaf extract had an antibacterial effect on the growth of S. mutans. We used turbidimetry, UV-Vis spectrophotometer, and two times of treatment to obtain the MIC of gedi leaf extract on Streptococcus mutans which was 6.25%. Conclusion: Gedi leaf extract could inhibit the growth of S. mutans with a MIC of 6.25%.Keywords: dental caries, gedi leaf extract (Abelmoschus manihot L.), Streptococcus mutans Abstrak: Streptococcus mutans merupakan bakteri yang paling banyak menyebabkan karies gigi karena bakteri ini berkemampuan memfermentasi karbohidrat menjadi asam yang berakibat turunnya pH pada permukaan gigi. Pencegahan karies gigi dapat dicapai dengan menghambat pertumbuhan bakteri kariogenik. Berbagai upaya dilakukan untuk mengen-dalikan dan mencegah bakteri kariogenik, antara lain dengan menggunakan bahan herbal; salah satunya yaitu tanaman gedi (Abelmoschus manihot L.). Daun gedi mengandung senyawa bioaktif antara lain flavonoid, alkaloid, steroid, dan saponin. Penelitian ini bertujuan untuk membuktikan efek inhibisi ekstrak daun gedi terhadap pertumbuhan S. mutans dan mendapatkan konsentrasi hambat minimum (KHM) ekstrak daun gedi terhadap pertumbuhan bakteri S. mutans. Jenis penelitian ini ialah eksperimental murni dengan randomized pretest-posttest control group design. Ekstrak daun gedi dibuat dengan metode maserasi dengan menggunakan etanol 96%. Hasil penelitian menunjukkan bahwa ekstrak daun gedi (Abelmoschus manihot L.) memiliki efek antibakteri dalam menghambat pertumbuhan bakteri Streptococcus mutans. Dengan menggunakan metode turbidimetri dan spektrofotometer UV-Vis dalam 2 (dua) kali perlakuan maka diperoleh KHM ekstrak daun gedi (Abelmoschus manihot L.) terhadap bakteri Streptococcus mutans terdapat pada konsentrasi 6,25%. Simpulan: Ekstrak daun gedi dapat meghambat pertumbuhan Streptococcus mutans dengan KHM pada konsentrasi 6,25%.Kata kunci: karies gigi, ekstrak daun gedi (Abelmoschus manihot L.), Streptococcus mutans

scholarly journals Astilbin Inhibits the Activity of Sortase A from Streptococcus mutans

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 465 ◽  
Author(s):  
Junxian Wang ◽  
Yan Shi ◽  
Shisong Jing ◽  
Haisi Dong ◽  
Dacheng Wang ◽  
...  
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Cell Attachment ◽  
Surface Proteins ◽  
Dynamics Simulation ◽  
Sortase A ◽  
Acid Fermentation ◽  
Host Cell Attachment ◽  
Potent Inhibitory Activity

Streptococcus mutans (S. mutans) is the primary etiological agent of dental caries. The S. mutans enzyme sortase A (SrtA) is responsible for anchoring bacterial cell wall surface proteins involved in host cell attachment and biofilm formation. Thus, SrtA is an attractive target for inhibiting dental caries caused by S. mutans-associated acid fermentation. In this study, we observed that astilbin, a flavanone compound extracted from Rhizoma Smilacis Glabrae, has potent inhibitory activity against the S. mutans SrtA, with an IC50 of 7.5 μg/mL. In addition, astilbin was proven to reduce the formation of biofilm while without affecting the growth of S. mutans. The results of a molecular dynamics simulation and a mutation analysis revealed that the Arg213, Leu111, and Leu116 of SrtA are important for the interaction between SrtA and astilbin. The results of this study demonstrate the potential of using astilbin as a nonbactericidal agent to modulate pathogenicity of S. mutans by inhibiting the activity of SrtA.

scholarly journals Novel Synthetic Antimicrobial Peptides against Streptococcus mutans

2007 ◽  
Vol 51 (4) ◽  
pp. 1351-1358 ◽  
Author(s):  
Jian He ◽  
Randal Eckert ◽  
Thanh Pharm ◽  
Maurice D. Simanian ◽  
Chuhong Hu ◽  
...  
Keyword(s):  
Dental Caries ◽  
Antimicrobial Peptides ◽  
Streptococcus Mutans ◽  
Peptide Libraries ◽  
Tooth Surface ◽  
Fusion Peptides ◽  
Biochemical Characteristics ◽  
Killing Activity ◽  
Constrained Peptides ◽  
Synthetic Antimicrobial Peptides

ABSTRACT Streptococcus mutans, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against S. mutans. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these “fusion” peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against S. mutans, several of which may be likely candidates for the development of anticaries agents.

pH Response and Tooth Surface Solubility at the Tooth/Bacteria Interface

2017 ◽  
Vol 51 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Gen Mayanagi ◽  
Koei Igarashi ◽  
Jumpei Washio ◽  
Nobuhiro Takahashi
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Polymethyl Methacrylate ◽  
Proteolytic Activity ◽  
Tooth Surface ◽  
Ph Response ◽  
Mineral Solubility ◽  
Experimental Apparatus ◽  
Root Dentin ◽  
Dissolved Components

Evaluating the physiochemical processes at the tooth surface/bacteria interface is important for elucidating the etiology of dental caries. This study aimed to compare the mineral solubility and protein degradation of coronal enamel (CE) and root dentin (RD), and investigate the involvement of dissolved components in bacteria-induced pH changes using a model of tooth/bacteria interface. An experimental apparatus forming a well was made of polymethyl methacrylate, and a bovine tooth (CE or RD) specimen was fixed at the bottom of the well. A miniature pH electrode was placed on the tooth, and Streptococcus mutans NCTC 10449 cells, grown in 0.5% glucose-containing complex medium, were packed into the well. The pH at the tooth/S. mutans interface was monitored continuously for 120 min after the addition of 0.5% glucose at 37°C. S. mutans cells were recovered from the wells, and the amounts of lactate and calcium were measured using a portable lactate meter and a fluorescent dye, respectively. Proteolytic activity was also evaluated fluorometrically. The pH of the RD/S. mutans interface was significantly higher than that of the CE/S. mutans interface (30 min: 6.37 ± 0.12 vs. 6.18 ± 0.11, 60 min: 6.08 ± 0.14 vs. 5.66 ± 0.27, 90 min: 5.49 ± 0.24 vs. 5.14 ± 0.22, p < 0.05). Greater amounts of calcium were dissolved from RD (3.19 ± 0.74 µg/mL) than from CE (1.84 ± 0.68 µg/mL; p < 0.05), while similar amounts of lactate were produced. Proteolytic activity was not detected at any of the interfaces. These results indicate that RD is more soluble to bacteria-induced acidification than CE. This method can contribute to the evaluation and development of caries-preventive materials.

scholarly journals Avaliação in vitro da Atividade Antimicrobiana de Extrato Alcoólico de Própolis Comparado à Solução de Clorexidina 0,12%

2017 ◽  
Vol 19 (2) ◽  
pp. 95
Author(s):  
Maria Paula Jacobucci Botelho ◽  
Amanda Da Silva ◽  
Fernanda Da Conceição Antônio Ferreira ◽  
Lígia Maria Molinari Capel
Keyword(s):  
Drinking Water ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Positive Control ◽  
Negative Control ◽  
Tooth Surface ◽  
Dental Biofilm ◽  
Fermentable Carbohydrates ◽  
Broad Understanding

Apesar dos esforços e do amplo entendimento sobre a cárie dental, está continua bastante prevalente em determinados segmentos da população. A doença apresenta etiologia multifatorial, com a dieta e os micro-organismos envolvidos desenvolvendo papéis fundamentais. Os Streptococcus mutans têm papel fundamental em seu início e é ubíquo em crianças a partir dos sete anos de idade. Para controlar essas bactérias é preciso uma dieta com baixo consumo de sacarose e de carboidratos fermentáveis, o que nem sempre se consegue. Sua remoção da superfície dentária só é possível por meio da fricção mecânica, mas pode-se prevenir sua presença no biofilme dentário através da utilização de antissépticos. O mais utilizado na Odontologia é a clorexidina, porém como não é isenta de efeitos adversos, atualmente, vêm-se estudando produtos alternativos, dentre os quais alguns agentes fitoterápicos. O objetivo deste trabalho foi analisar a atividade da própolis contra os S. mutans em relação à clorexidina. Foi analisada própolis 70% diluída em álcool 96% e após diluída em água potável 5ml, própolis 50%, própolis 12% e clorexidina 0,12% (controle positivo), e solução salina (controle negativo). O operador foi cego em relação às substâncias que estava utilizando. Somente a clorexidina 0.12% e a própolis 12% apresentaram halo de inibição claro. Neste estudo, a clorexidina apresentou melhor atividade contra os S.mutans.Palavras-chave: Clorexidina. Cárie Dentária. Streptococcus mutans.AbstractDespite the efforts and the broad understanding on dental caries, it is still quite prevalent in certain segments of the population. The disease shows a multifactorial etiology, with diet and microorganisms involved developing fundamental roles. The Streptococcus mutans has key role in its beginning and is ubiquitous in children as young as seven years of age. To control these bacteria a diet is necessary with low consumption of sucrose and of fermentable carbohydrates, which is not always possible. The tooth surface removal is only possible through mechanical friction, but it is possible to prevent the presence of dental biofilm through the use of antiseptics. The most widely used in dentistry is chlorhexidine, however as it is not devoid of adverse effects, currently alternative products have been studying, among which some herbal agents. The aim of this study was to analyze the activity of propolis against S. mutans compared to chlorhexidine. Propolis was analyzed diluted in 70% ethanol 96% and further diluted in drinking water 5ml, 50% propolis, propolis 12% and 0.12% chlorhexidine (positive control), and saline (negative control). The operator was blinded for the substances he was using. Only 0.12% chlorhexidine and 12% propolis showed clear inhibition halo. In this study the chlorhexidine presented better activity against S. mutans.Keywords: Chlorhexidine. Dental Caries. Antimicrobials. Streptococcus mutans

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