Arginine-induced metabolomic perturbation in Streptococcus mutans.
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ABSTRACT: Background
Streptococcus mutans is a major pathogen responsible for dental caries. Arginine is a promising potential caries preventive agent which can inhibit the growth of S. mutans. However, the mechanism whereby arginine inhibits S. mutans growth remains unclear.Aim
To assess the impact of arginine-induced metabolomic perturbations on S. mutans under biofilm conditions.Methods
We identified 5,933 and 7,413 ions in positive (ESI+) and negative (ESI-) electrospray ion modes, respectively, with a total of 11.05% and 11.58% differential ions subsequently detected in two respective modes. Further analyses of these metabolites led to identification of 8 and 22 metabolic pathways that were affected by arginine treatment in ESI+ and ESI- modes.Results
Once or twice daily treatments of S. mutans biofilms with arginine resulted in reductions in biofilm biomass. Significant reductions in EPS production were observed following twice daily arginine treatments. Identified metabolites that were significantly differentially abundant following arginine treatment were associated with glycolysis metabolism, amino sugar and nucleotide sugar metabolism, and peptidoglycan synthesis.Conclusions
Arginine can reduce S. mutans biofilm growth and acid production by inhibiting glycolysis, amino sugar and nucleotide sugar metabolism, and peptidoglycan synthesis.
SUBMITTER: Liu Y
PROVIDER: S-EPMC8745357 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Arginine-induced metabolomic perturbation in <i>Streptococcus mutans</i>.
Liu Yudong Y Liu Shanshan S Zhi Qinghui Q Zhuang Peilin P Zhang Rongxiu R Zhang Zhenzhen Z Zhang Kai K Sun Yu Y
Journal of oral microbiology 20220107 1
<h4>Background</h4><i>Streptococcus mutans</i> is a major pathogen responsible for dental caries. Arginine is a promising potential caries preventive agent which can inhibit the growth of <i>S. mutans</i>. However, the mechanism whereby arginine inhibits <i>S. mutans</i> growth remains unclear.<h4>Aim</h4>To assess the impact of arginine-induced metabolomic perturbations on <i>S. mutans</i> under biofilm conditions.<h4>Methods</h4>We identified 5,933 and 7,413 ions in positive (ESI+) and negativ ...[more]
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Project description:<h4><strong>BACKGROUND: </strong><em>Streptococcus mutans</em> is a major pathogen responsible for dental caries. Arginine is a promising potential caries preventive agent which can inhibit the growth of <em>S. mutans</em>. However, the mechanism whereby arginine inhibits <em>S. mutans</em> growth remains unclear.</h4><h4><strong>AIM: </strong>To assess the impact of arginine-induced metabolomic perturbations on <em>S. mutans</em> under biofilm conditions.</h4><h4><strong>METHODS: </strong>We identified 5,933 and 7,413 ions in positive (ESI+) and negative (ESI-) electrospray ion modes, respectively, with a total of 11.05% and 11.58% differential ions subsequently detected in two respective modes. Further analyses of these metabolites led to identification of 8 and 22 metabolic pathways that were affected by arginine treatment in ESI+ and ESI- modes.</h4><h4><strong>RESULTS: </strong>Once or twice daily treatments of <em>S. mutans</em> biofilms with arginine resulted in reductions in biofilm biomass. Significant reductions in EPS production were observed following twice daily arginine treatments. Identified metabolites that were significantly differentially abundant following arginine treatment were associated with glycolysis metabolism, amino sugar and nucleotide sugar metabolism, and peptidoglycan synthesis.</h4><h4><strong>CONCLUSIONS: </strong>Arginine can reduce <em>S. mutans</em> biofilm growth and acid production by inhibiting glycolysis, amino sugar and nucleotide sugar metabolism, and peptidoglycan synthesis.</h4>
2023-10-20 | MTBLS3020 | MetaboLights
Project description:Streptococcus mutans is a primary cariogenic pathogen in humans. Arginine metabolism is required for bacterial growth. In S. mutans, however, the involvement of transcription factors in regulating arginine metabolism is unclear. The purpose of this study was to investigate the function and mechanism of ArgR family transcription factors in S. mutans. Here, we identified an ArgR (arginine repressor) family transcription factor named AhrC, which negatively regulates arginine biosynthesis and biofilm formation in S. mutans. The ahrC in-frame deletion strain exhibited slow growth and significantly increased intracellular arginine content. The strain overexpressing ahrC showed reduced intracellular arginine content, decreased biofilm biomass, reduced production of water-insoluble exopolysaccharides (EPS), and different biofilm structures. Furthermore, global gene expression profiles revealed differential expression levels of 233 genes in the ahrC-deficient strain, among which genes related to arginine biosynthesis (argJ, argB, argC, argD, argF, argG, argH) were significantly upregulated. In the ahrC overexpression strain, there are 89 differentially expressed genes, mostly related to arginine biosynthesis. The conserved DNA patterns bound by AhrC were identified by electrophoretic mobility shift assay (EMSA) and DNase I footprinting. In addition, the analysis of β-galactosidase activity showed that AhrC acted as a negative regulator. Taken together, our findings suggest that AhrC is an important transcription factor that regulates arginine biosynthesis gene expression and biofilm formation in S. mutans. These findings add new aspects to the complexity of regulating the expression of genes involved in arginine biosynthesis and biofilm formation in S. mutans. IMPORTANCE Arginine metabolism is essential for bacterial growth. The regulation of intracellular arginine metabolism in Streptococcus mutans, one of the major pathogens of dental caries, is unclear. In this study, we found that the transcription factor AhrC can directly and negatively regulate the expression of N-acetyl-gamma-glutamyl-phosphate reductase (argC), thus regulating arginine biosynthesis in S. mutans. In addition, the ahrC overexpression strain exhibited a significant decrease in biofilm and water-insoluble extracellular polysaccharides (EPS). This study adds new support to our understanding of the regulation of intracellular arginine metabolism in S. mutans.
| S-EPMC9430756 | biostudies-literature
Project description:Streptococcus mutans is a common constituent of oral biofilms and a primary etiologic agent of human dental caries. The bacteria associated with dental caries have potent abilities to produce organic acids from dietary carbohydrates and to grow and metabolize in acidic conditions. By contrast, many commensal bacteria produce ammonia through the arginine deiminase system (ADS), which moderates the pH of oral biofilms. Arginine metabolism by the ADS is a significant deterrent to the initiation and progression of dental caries. In this study, we observed how exogenously provided l-arginine affects the growth, the virulence properties, and the tolerance of environmental stresses of S. mutans Supplementation with 1.5% arginine (final concentration) had an inhibitory effect on the growth of S. mutans in complex and chemically defined media, particularly when cells were exposed to acid or oxidative stress. The genes encoding virulence factors required for attachment/accumulation (gtfB and spaP), bacteriocins (nlmA, nlmB, nlmD, and cipB), and the sigma factor required for competence development (comX) were downregulated during growth with 1.5% arginine. Deep sequencing of RNA (RNA-Seq) comparing the transcriptomes of S. mutans growing in chemically defined media with and without 1.5% arginine revealed differential expression of genes encoding ATP-binding cassette transporters, metal transporters, and constituents required for survival, metabolism, and biofilm formation. Therefore, the mechanisms of action by which arginine inhibits dental caries include direct adverse effects on multiple virulence-related properties of the most common human dental caries pathogen.IMPORTANCE Metabolism of the amino acid arginine by the arginine deiminase system (ADS) of certain oral bacteria raises the pH of dental plaque and provides a selective advantage to health-associated bacteria, thereby protecting the host from dental caries (cavities). Here, we examine the effects of arginine on the cavity-causing bacterium Streptococcus mutans We find that arginine negatively impacts the growth, the pathogenic potential, and the tolerance of environmental stresses in a way that is likely to compromise the ability of S. mutans to cause disease. Using genetic and genomic techniques, multiple mechanisms by which arginine exerts its influence on virulence-related properties of S. mutans are discovered. This report demonstrates that a primary mechanism of action by which arginine inhibits the initiation and progression of dental caries may be by reducing the pathogenic potential of S. mutans.
| S-EPMC5514675 | biostudies-literature
Project description:Unlabelledl-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous l-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, l-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous l-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) l-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical l-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, l-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H2O2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H2O2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of l-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor.ImportanceDental caries is one of the most prevalent and costly infectious diseases worldwide, caused by a biofilm formed on tooth surfaces. Novel strategies that compromise the ability of virulent species to assemble and maintain pathogenic biofilms could be an effective alternative to conventional antimicrobials that indiscriminately kill other oral species, including commensal bacteria. l-Arginine at 1.5% has been shown to be clinically effective in modulating cariogenic biofilms via alkali production by arginolytic bacteria. Using a mixed-species ecological model, we show new mechanisms by which l-arginine disrupts the process of biofilm matrix assembly and the dynamic microbial interactions that are associated with cariogenic biofilm development, without impacting the bacterial viability. These results may aid in the development of enhanced methods to control biofilms using l-arginine.
| S-EPMC5019072 | biostudies-literature
Project description:Streptococcus mutans is a common constituent of oral biofilms and a primary etiologic agent of human dental caries. The bacteria associated with dental caries have a potent ability to produce organic acids from dietary carbohydrates and to grow and metabolize in acidic conditions. In this study, we observed supplementation with 1.5% arginine (final concentration) had inhibitory effects on the growth of S. mutans in complex and chemically defined media, particularly when cells were exposed to acid or oxidative stress. Deep-sequencing of RNA (RNA-Seq) comparing the transcriptomes of S. mutans growing in a chemically defined medium with and without 1.5% arginine in neutral and acidic pH conditions and under oxidative stress conditions revealed interesting results. The results provide new insights into the mechanisms of action by which arginine inhibits dental caries through direct adverse effects on multiple virulence-related properties of the most common human dental caries pathogen. The findings significantly enhance our understanding of the genetics and physiology of this cariogenic pathogen.
2017-05-20 | GSE98020 | GEO
Project description:Competence-stimulating-peptide (CSP)-mediated competence development in Streptococcus mutans is a transient and biphasic process, since only a subpopulation induces the expression of ComX in the presence of CSP, and the activation of the DNA uptake machinery in this fraction shuts down ~3 to 4 h postinduction. Here, we combine for the first time, to our knowledge, the bacterial flow-cytometric sorting of cells and subpopulation-specific transcriptome analysis of both the competent and noncompetent fraction of CSP-treated S. mutans cells. Sorting was guided by a ComX-green fluorescent protein (ComX-GFP) reporter, and the transcriptome analysis demonstrated the successful combination of both methods, because a strong enrichment of transcripts for comX and its downstream genes was achieved. Three two-component systems were expressed in the competent fraction, and among them was ComDE. Moreover, the recently identified regulator system ComR/S was expressed exclusively in the competent fraction. In contrast, the expression of bacteriocin-related genes was at the same level in all cells. GFP reporter strains for ComE and CipB (mutacin V) confirmed this expression pattern on the single-cell level. Fluorescence microscopy revealed that some ComX-expressing cells committed autolysis in an early stage of competence initiation. In viable ComX-expressing cells, the uptake of DNA could be shown on the single-cell level. This study demonstrates that all cells in the population respond to CSP through the activation of bacteriocin-related genes. Some of these cells start to activate ComX expression but then segregate into two subpopulations, one becoming competent and another one that lyses, resulting in intrapopulation diversity.
| S-EPMC3133041 | biostudies-literature
Project description:Saliva protects dental surfaces against cavities (i. e., dental caries), a highly prevalent infectious disease frequently associated with acidogenic Streptococcus mutans. Substantial in vitro evidence supports amylase, a major constituent of saliva, as either protective against caries or supporting caries. We therefore produced mice with targeted deletion of salivary amylase (Amy1) and determined the impact on caries in mice challenged with S. mutans and fed a diet rich in sucrose to promote caries. Total smooth surface and sulcal caries were 2.35-fold and 1.79-fold greater in knockout mice, respectively, plus caries severities were twofold or greater on sulcal and smooth surfaces. In in vitro experiments with samples of whole stimulated saliva, amylase expression did not affect the adherence of S. mutans to saliva-coated hydroxyapatite and slightly increased its aggregation in solution (i.e., oral clearance). Conversely, S. mutans in biofilms formed in saliva with 1% glucose displayed no differences when cultured on polystyrene, but on hydroxyapatite was 40% less with amylase expression, suggesting that recognition by S. mutans of amylase bound to hydroxyapatite suppresses growth. However, this effect was overshadowed in vivo, as the recoveries of S. mutans from dental plaque were similar between both groups of mice, suggesting that amylase expression helps decrease plaque acids from S. mutans that dissolve dental enamel. With amylase deletion, commensal streptococcal species increased from ~75 to 90% of the total oral microbiota, suggesting that amylase may promote higher plaque pH by supporting colonization by base-producing oral commensals. Importantly, collective results indicate that amylase may serve as a biomarker of caries risk.
| S-EPMC8283412 | biostudies-literature
Project description:Streptococcus gordonii and Streptococcus mutans avidly colonize teeth. S. gordonii glucosyltransferase (GtfG) and amylase-binding proteins (AbpA/AbpB), and S. mutans glucosyltransferase (GtfB), affect their respective oral colonization abilities. We investigated their interrelationships and caries association in a rat model of human caries, examining the sequence of colonization and non- vs. high-sucrose diets, the latter being associated with aggressive decay in humans and rats. Virulence-characterized wild-types of both species and well-defined mutants of S. gordonii with interrupted abpA and gtfG genes were studied. While both S. gordonii and S. mutans were abundant colonizers of rat's teeth in the presence of either diet, if inoculated singly, S. mutans always out-competed S. gordonii on the teeth, independent of diet, strain of S. mutans, simultaneous or sequential inoculation, or presence/absence of mutations of S. gordonii's abpA and gtfG genes known to negatively or positively affect its colonization and to interact in vitro with S. mutans GtfB. S. mutans out-competed S. gordonii in in vivo plaque biofilm. Caries induction reflected S. mutans or S. gordonii colonization abundance: the former highly cariogenic, the latter not. S. gordonii does not appear to be a good candidate for replacement therapy. These results are consistent with human data.
| S-EPMC3327732 | biostudies-literature
Project description:In the human pathogen Streptococcus mutans, the canonical peptide-based quorum sensing system is an inducible DNA repair system that is pivotal for bacterial survival. Previous work showed that the CSP signaling peptide is a stress-signaling alarmone that controls different stress-induced phenotypes. In this study, we exposed S. mutans to the CSP pheromone to mimic DNA damage conditions. Transcriptome analysis was then performed to evaluate the differential gene expression between the normal stationary phase cells and the CSP-induced stationary phase cells. The data obtained contribute to the understanding of the CSP-induced phenotypes in S. mutans.
2024-04-28 | GSE264670 | GEO
Project description:BackgroundTo investigate the inhibition mechanism of copper ions on Streptococcus mutans-Veillonella parvula dual biofilm.MethodsS. mutans-V. parvula dual biofilm was constructed and copper ions were added at different concentrations. After the biofilm was collected, RNA-seq and qRT-PCR were then performed to get gene information.ResultsThe coculture of S. mutans and V. parvula formed a significantly better dual biofilm of larger biomass than S. mutans mono biofilm. And copper ions showed a more significant inhibitory effect on S. mutans-V. parvula dual biofilm than on S. mutans mono biofilm when copper ions concentration reached 100 µM, and copper ions showed a decreased inhibitory effect on S. gordonii-V. parvula dual biofilm and S. sanguis-V.parvula dual biofilm than on the two mono biofilms as the concentration of copper ions increased. And common trace elements such as iron, magnesium, and zinc showed no inhibitory effect difference on S. mutans-V. parvula dual biofilm. The RNA-seq results showed a significant difference in the expression of a new ABC transporter SMU_651c, SMU_652c, SMU_653c, and S. mutans copper chaperone copYAZ. SMU_651c, SMU_652c, and SMU_653c were predicted to function as nitrite/nitrate transporter-related proteins, which suggested the specific inhibition of copper ions on S. mutans-V. parvula dual biofilm may be caused by the activation of S. mutans reactive nitrogen species.ConclusionsStreptococcus mutans and Veillonella parvula are symbiotic, forming a dual biofilm of larger biomass to better resist the external antibacterial substances, which may increase the virulence of S. mutans. While common trace elements such as iron, magnesium, and zinc showed no specific inhibitory effect on S. mutans-V. parvula dual biofilm, copper ion had a unique inhibitory effect on S. mutans-V. parvula dual biofilm which may be caused by activating S. mutans RNS when copper ions concentration reached 250 µM.
| S-EPMC9883903 | biostudies-literature