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.

Insights into the biochemical and functional characterization of sortase E transpeptidase of Corynebacterium glutamicum

2019 ◽  
Vol 476 (24) ◽  
pp. 3835-3847 ◽  
Author(s):  
Aliyath Susmitha ◽  
Kesavan Madhavan Nampoothiri ◽  
Harsha Bajaj
Keyword(s):  
Protein Engineering ◽  
Cell Attachment ◽  
Functional Characterization ◽  
Protein Structures ◽  
Structural Similarity ◽  
Surface Proteins ◽  
Sortase A ◽  
Peptide Cleavage ◽  
New Findings

Most Gram-positive bacteria contain a membrane-bound transpeptidase known as sortase which covalently incorporates the surface proteins on to the cell wall. The sortase-displayed protein structures are involved in cell attachment, nutrient uptake and aerial hyphae formation. Among the six classes of sortase (A–F), sortase A of S. aureus is the well-characterized housekeeping enzyme considered as an ideal drug target and a valuable biochemical reagent for protein engineering. Similar to SrtA, class E sortase in GC rich bacteria plays a housekeeping role which is not studied extensively. However, C. glutamicum ATCC 13032, an industrially important organism known for amino acid production, carries a single putative sortase (NCgl2838) gene but neither in vitro peptide cleavage activity nor biochemical characterizations have been investigated. Here, we identified that the gene is having a sortase activity and analyzed its structural similarity with Cd-SrtF. The purified enzyme showed a greater affinity toward LAXTG substrate with a calculated KM of 12 ± 1 µM, one of the highest affinities reported for this class of enzyme. Moreover, site-directed mutation studies were carried to ascertain the structure functional relationship of Cg-SrtE and all these are new findings which will enable us to perceive exciting protein engineering applications with this class of enzyme from a non-pathogenic microbe.

scholarly journals Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3170 ◽  
Author(s):  
Vika Gabe ◽  
Tomas Kacergius ◽  
Saleh Abu-Lafi ◽  
Mouhammad Zeidan ◽  
Basheer Abu-Farich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Colorimetric Method ◽  
Solid Surfaces ◽  
Dependent Manner ◽  
Oral Diseases ◽  
Expression Change ◽  
Biofilm Development

The accumulation of biofilm by Streptococcus mutans bacteria on hard tooth tissues leads to dental caries, which remains one of the most prevalent oral diseases. Hence, the development of new antibiofilm agents is of critical importance. The current study reports the results from testing the effectiveness of octyl gallate (C8-OG) against: (1) S. mutans biofilm formation on solid surfaces (polystyrene, glass), (2) acidogenicity, (3) and the expression of biofilm-related genes. The amount of biofilm formed by S. mutans bacteria was evaluated using the colorimetric method and optical profilometry. The pH of the biofilm growth medium was measured with microelectrode. A quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the expression of genes encoding glucan binding protein B (gbpB), glucosyltransferases B, -C, -D (gtfB, -C, -D), and the F-ATPase β subunit of the F1 protein (atpD). The results show that C8-OG significantly diminished biofilm formation by exposed S. mutans on solid surfaces and suppressed acidogenicity in a dose-dependent manner, compared to unexposed bacteria (p < 0.05). The C8-OG concentration of 100.24 µM inhibited S. mutans biofilm development on solid surfaces by 100% and prevented a decrease in pH levels by 99%. In addition, the RT-qPCR data demonstrate that the biofilm-producing bacteria treated with C8-OG underwent a significant reduction in gene expression in the case of the four genes under study (gbpB, gtfC, gtfD, and atpD), and there was a slight decrease in expression of the gtfB gene. However, C8-OG treatments did not produce significant expression change compared to the control for the planktonic cells, although there was a significant increase for the atpD gene. Therefore, C8-OG might be a potent antibiofilm and/or anticaries agent for oral formulations that aim to reduce the prevalence of dental caries.

scholarly journals Baicalein Inhibits Streptococcus mutans Biofilms and Dental Caries-Related Virulence Phenotypes

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 215
Author(s):  
Aparna Vijayakumar ◽  
Hema Bhagavathi Sarveswari ◽  
Sahana Vasudevan ◽  
Karthi Shanmugam ◽  
Adline Princy Solomon ◽  
...  
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Acid Production ◽  
Cell Surface Hydrophobicity ◽  
Surface Hydrophobicity ◽  
Oral Disease ◽  
Public Healthcare ◽  
Surface Attachment ◽  
First Time

Dental caries, the most common oral disease, is a major public healthcare burden and affects more than three billion people worldwide. The contemporary understanding of the need for a healthy microbiome and the emergence of antimicrobial resistance has resulted in an urgent need to identify compounds that curb the virulence of pathobionts without microbial killing. Through this study, we have demonstrated for the first time that 5,6,7-trihydroxyflavone (Baicalein) significantly downregulates crucial caries-related virulence phenotypes in Streptococcus mutans. Baicalein significantly inhibited biofilm formation by Streptococcus mutans UA159 (MBIC50 = 200 μM), without significant growth inhibition. Notably, these concentrations of baicalein did not affect the commensal S. gordonii. Strikingly, baicalein significantly reduced cell surface hydrophobicity, autoaggregation and acid production by S. mutans. Mechanistic studies (qRT-PCR) showed downregulation of various genes regulating biofilm formation, surface attachment, quorum sensing, acid production and competence. Finally, we demonstrate the potential translational value of baicalein by reporting synergistic interaction with fluoride against S. mutans biofilms.

Anti-Biofilm Formation of Streptococcus mutans by Jasmine Mouthwash

2018 ◽  
Vol 773 ◽  
pp. 323-327
Author(s):  
Sroisiri Thaweboon ◽  
Boonyanit Thaweboon
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Antimicrobial Activities ◽  
Inhibitory Effect ◽  
Negative Control ◽  
Oral Streptococci ◽  
Drug Of Choice ◽  
Causative Microorganism ◽  
Warm Temperate

Streptococcus mutans has been reported to be a major causative microorganism for oral biofilm associated with dental caries. Jasmine sambac or Arabian jasmine is a species of jasmine native to tropical and warm temperate regions particularly West and Southeast Asia. The antimicrobial activities of essential oil extracted from the flowers of J. sambac have been shown to attract researchers. Objective: To determine the anti-biofilm formation of S. mutans by mouthwash containing jasmine oil. Materials and Methods: S. mutans KPSK2, the cariogenic strain of oral streptococci was used in the study. The 24-h biofilms of S. mutans were formed on polystyrene plates treated with jasmine mouthwash. The 0.2% chlorhexidine gluconate and phosphate buffer saline mouthwash were used as a positive and negative control respectively. The amount of biofilm was quantified by crystal violet staining and spectrophotometry at an optical density of 595 nm. Results: Jasmine mouthwash showed a significant inhibitory effect on S. mutans biofilm formation by decreasing 43% of biofilm whereas that of chlorhexidine showed 71% reduction. Conclusion: The anti-biofilm formation property of jasmine mouthwash was elucidated; therefore it might be another drug of choice that can be used as an adjunct to control the oral health in the prevention of dental caries.

Anti-biofilm activity of α-mangostin isolated from Garcinia mangostana L.

2015 ◽  
Vol 70 (11-12) ◽  
pp. 313-318
Author(s):  
Phuong T.M. Nguyen ◽  
Bac H. Vo ◽  
Nhung T. Tran ◽  
Quyen D. Van
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Causative Agent ◽  
Biofilm Formation ◽  
Vehicle Control ◽  
Garcinia Mangostana ◽  
Key Enzymes ◽  
Surface Activities ◽  
Topical Applications

Abstract This study was carried out to further examine the anti-biofilm activity of α-mangostin (αMG) isolated from Garcinia mangostana L. grown in Vietnam, against a strongly biofilm producing Streptococcus mutans, a major causative agent of dental caries. The obtained data indicated that topical applications (twice-daily, 60 s exposure each) of 150 μM αMG during biofilm formation on the surfaces of hydroxyapatite disks (sHA) by S. mutans UA159 resulted in 30.7% reduction in biofilm accumulation after 68 h of growth. The treatment did not affect the viability of S. mutans cells in the biofilms. The surface activities of two key enzymes responsible for biofilm formation, i.e. the glycosyltransferases GtfB and GtfC, were reduced by 20 and 35%, respectively (vs. vehicle control, P < 0.05). Interestingly, αMG specifically targeted S. mutans in mixed biofilms, resulting in the decrease of the S. mutans population and total biofilm biomass. αMG was also found to accumulate within the biofilm of S. mutans up to 4.5 μg/biofilm, equal to a concentration of >10 μM/biofilm. In conclusion, this study confirmed anti-biofilm activity of αMG against S. mutans. A brief exposure to αMG may suppress biofilm formation by targeting key enzymes imvolved in biofilm formation.

scholarly journals Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV

2017 ◽  
Vol 199 (8) ◽  
Author(s):  
Manoharan Shankar ◽  
Mohammad S. Hossain ◽  
Indranil Biswas
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Normal Growth ◽  
Hypothetical Protein ◽  
Bacteriocin Production ◽  
Transcript Levels ◽  
Content Type ◽  
Tooth Surfaces

ABSTRACT Streptococcus mutans, an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque. S. mutans expresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. An S. mutans strain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of the S. mutans genes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene as sprV (streptococcal pleiotropic regulator of virulence). The transcript levels of several relevant genes in the sprV mutant corroborated the phenotypes observed upon sprV deletion. Owing to its highly conserved nature, inactivation of the sprV ortholog in Streptococcus gordonii also resulted in poor growth and defective UV tolerance and competence development as in the case of S. mutans. Our experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in the S. mutans biology. IMPORTANCE Streptococcus mutans employs several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are critical for successful disease establishment. Sometimes these regulators, which are potential targets for antimicrobials, are lost in the genomic context due to the lack of annotated homologs. This work outlines the regulatory impact of a small, highly conserved hypothetical protein, SprV, encoded by S. mutans. We show that SprV affects the transcript levels of various virulence factors required for normal growth, biofilm formation, stress tolerance, genetic competence, and bacteriocin production.

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 Green Tea Polyphenol Epigallocatechin-3-Gallate-Stearate Inhibits the Growth of Streptococcus mutans: A Promising New Approach in Caries Prevention

2018 ◽  
Vol 6 (3) ◽  
pp. 38 ◽  
Author(s):  
Amy Melok ◽  
Lee Lee ◽  
Siti Mohamed Yussof ◽  
Tinchun Chu
Keyword(s):  
Dental Caries ◽  
Oral Cavity ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Morphological Changes ◽  
The United States ◽  
Chlorhexidine Gluconate ◽  
Log Reduction ◽  
Colony Forming Units ◽  
Green Tea Polyphenol

Streptococcus mutans (S. mutans) is the main etiological bacteria present in the oral cavity that leads to dental caries. All of the S. mutans in the oral cavity form biofilms that adhere to the surfaces of teeth. Dental caries are infections facilitated by the development of biofilm. An esterified derivative of epigallocatechin-3-gallate (EGCG), epigallocatechin-3-gallate-stearate (EGCG-S), was used in this study to assess its ability to inhibit the growth and biofilm formation of S. mutans. The effect of EGCG-S on bacterial growth was evaluated with colony forming units (CFU) and log reduction; biofilm formation was qualitatively determined by Congo red assay, and quantitatively determined by crystal violet assay, fluorescence-based LIVE/DEAD assays to study the cell viability, and scanning electron microscopy (SEM) was used to evaluate the morphological changes. The results indicated that EGCG-S was able to completely inhibit growth and biofilm formation at concentrations of 250 µg/mL. Its effectiveness was also compared with a commonly prescribed mouthwash in the United States, chlorhexidine gluconate. EGCG-S was shown to be equally effective in reducing S. mutans growth as chlorhexidine gluconate. In conclusion, EGCG-S is potentially an anticariogenic agent by reducing bacterial presence in the oral cavity.

scholarly journals Inhibitory Effect ofBacillus velezensison Biofilm Formation byStreptococcus mutans

2018 ◽  
Author(s):  
Yesol Yoo ◽  
Dong-Ho Seo ◽  
Hyunjin Lee ◽  
Young-Do Nam ◽  
Myung-Ji Seo
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Culture Medium ◽  
Focal Point ◽  
Cell Surface Hydrophobicity ◽  
Surface Hydrophobicity ◽  
Inhibitory Effect ◽  
Fermented Foods ◽  
Bacillus Velezensis

ABSTRACTStreptococcus mutansplays a key role in the development of dental caries and promotes the formation of oral biofilm produced by glucosyltransferases (GTFs).Bacillus velezensisK68 was isolated from traditional fermented foods and inhibits biofilm formation mediated byS. mutans. Gene amplification results demonstrated thatB. velezensisK68 contained genes for the biosynthesis of 1-deoxynojirimycin (1-DNJ), a known GTF expression inhibitor. The presence of the GabT1, Yktc1, and GutB1 genes required for 1-DNJ synthesis inB. velezensisK68 was confirmed. Supernatant fromB. velezensisK68 culture medium inhibited biofilm formation by 84% whenS. mutanswas cultured for 48 h, and inhibited it maximally when 1% glucose was added to theS. mutansculture medium as a GTF substrate. In addition, supernatant fromB. velezensisK68 medium containing 3 ppb 1- DNJ decreasedS. mutanscell surface hydrophobicity by 79.0 ± 0.8% compared with that of untreated control. The supernatant containing 1-DNJ decreasedS. mutansadherence by 99.97% and 98.83% under sugar-dependent and sugar-independent conditions, respectively.S. mutanstreated with the supernatant exhibited significantly reduced expression of the essential GTF genesgtfB,gtfC,andgtfDcompared to that in the untreated group. Thus,B. velezensisinhibits the biofilm formation, adhesion, and GTF gene expression ofS. mutansthrough 1- DNJ production.IMPORTANCEDental caries is among the most common infectious diseases worldwide, and its development is closely associated with physiological factors of bacteria, such as the biofilm formation and glucosyltransferase production ofStreptococcus mutans.Biofilms are difficult to remove once they have formed due to the exopolysaccharide matrix produced by the microorganisms residing in them; thus, inhibiting biofilm formation is a current focal point of research into prevention of dental caries. This study describes the inhibitory properties ofBacillus velezensisK68, an organism isolated from traditional Korean fermented foods, against biofilm formation byS. mutans. Herein, we show thatB. velezensisinhibits the biofilm formation, adherence to surfaces, and glucosyltransferase production ofS. mutans.

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