Global transcriptional analysis of S. mutans metalloregulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Streptococcus mutans UA159
PROVIDER: GSE10215 | GEO | 2009/01/18
SECONDARY ACCESSION(S): PRJNA108337
REPOSITORIES: GEO
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Project description:Multiple S. mutans genes that are subject to SloR control are likely contributors to virulence. The regulation of these genes in response to metal ion limitation vs. availability in the oral cavity can significantly facilitate the caries-forming process and hence continued analysis of these data can reveal novel candidate genes for the purposes of therapeutic intervention and/or prevention. Keywords: Genetic modification, dose response, metalloregulation Analyses were based on a comparison between low Mn and high Mn groups (paired comparisons A, B, and C) and the monitoring of gene expression in the presence (WT) or absence (mutant) of SloR under moderate Mn content. Analysis of significance amongst all genes and the formulation of hypotheses that are relevant to the cariogenic state were performed.
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Project description:Childhood caries is an extremely common childhood chronic disease, affecting 60–90% of children in industrialized countries. It results in lesions in both the primary and permanent dentitions, hospitalizations and emergency room visits, high treatment costs, loss of school days, diminished ability to learn increases the risk of caries in adulthood. Streptococcus mutans is a key bacteria in caries development. While multiple caries risk factors have been identified, significant interpersonal variability not explained by known risk factors still exists. The immune system generates a personal antibody repertoire that helps maintain a balanced and healthy oral microbiome. Using mass-spectrometry, we probed in an hypothesis-free manner which S. mutans proteins are identified by antibodies of children with low and high DMFT (decayed, missing, filled teeth) scores. We identified a core set of proteins, recognized by the immune system of most individuals. This set was enriched with proteins enabling bacterial adhesion, and included glucosyltransferases and glucan-binding proteins known to be important for S. mutans cariogenicity. To explore the physiological relevance of these findings, we tested the ability of saliva from caries free individuals in preventing S. mutans from binding to the tooth surface. Indeed, saliva from individuals with caries free prevented S. mutans binding to teeth. These findings map the S. mutans proteome targeted by the immune system and suggest that inhibiting tooth attachment is a primary mechanism used by the immune system to maintain oral balance and prevent caries. These findings provide new insights into the role of the immune system in maintaining oral health and preventing caries development.
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Project description:Zinc is an essential divalent trace metal for living cells. Intracellular zinc homeostasis is critical to the pathogenicity and virulence of bacteria, however the strategies of zinc homeostasis maintain in Streptococcus mutans, an important causative pathogen of dental caries, is unknown. In this study, we examined the function of an ABC transporter AdcCBA and its transcription factor AdcR in S. mutans. Using RNA-Seq analysis, LacZ-reporter studies and gel mobility shift assay, we showed that a MarR family transcription factor AdcR directly regulates the activity of promoters of adcRCB and adcA in response to the concentration of zinc in their environmental niches. Deletion of adcR increases the sensitivity of S. mutans to excessive zinc supply. Taken together, our finding suggests that Adc regulon, consists of a zinc uptake transporter AdcCBA and a zinc-responsive repressor AdcR, plays a prominent role in the maintenance of intracellular zinc homeostasis of S. mutans.
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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.
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Project description:Streptococcus mutans and Candida albicans, as the most common bacterial and fungal in the oral cavity respectively, are considered as microbiological risk marker of early childhood caries. S. mutans MVs contain virulence proteins, which play a role in biofilm formation and disease progression. Our previous research found that S. mutans MVs harboring glucosyltransferases augment C. albicans biofilm formation through increasing the exopolysaccharide production, but the specific impact of S. mutans MVs on C. albicans virulence and pathogenicity is still unknown.
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Project description:Recent RNA-seq studies have given us a deeper insight into the cariogenic impact of carbohydrate sources in the bacterium Streptococcus mutans, the principal etiological agent of human dental caries. The process of dental caries development is given by the ability of this bacterium to ferment some carbohydrates up to organic acids contributing to the pH decrease in the oral cavity and the demineralization of the enamel. Besides, in dental caries progression, an important role is played by biofilm formation, which starts and ends with free planktonic cells, and it is given by several unique properties called virulence factors. The most cariogenic carbohydrate is considered sucrose, an easily metabolizable source of energy inducing acidification and synthesis of glucans forming typical bacterial cell clumps. By using multifaceted methodological approaches, we compared the transcriptomic and metabolomic profiles of S. mutans growing in planktonic culture on preferred and non-preferred carbohydrates and fasting conditions. Lactose and xylitol showed high effectiveness in the regulation of the IPS metabolism, cell wall structure and overall virulence involved in the initial phase of biofilm formation and structure but with an opposite pattern compared to sucrose and glucose. These findings confirm the recent results that xylitol and lactose play a vital role in biofilm structure but do not reduce its formation related to their cariogenic potential.
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Project description:To gain further insights into the molecular basis of the effects of oxygen on biofilm formation by S. mutans (Ahn and Burne, 2007), we used DNA microarrays to analyze gene expression profiles of cells cultured under aerobic or anaerobic conditions. Keywords: Oxygen, Biofilm, Caries, Microarray
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Project description:Dental caries are closely associated with the virulence of Streptococcus mutans. The virulence expression of S. mutans is linked to its stress adaptation to the changes in the oral environment. In this work we used whole-genome microarrays to profile the dynamic transcriptomic responses of S. mutans during physiological heat stress. In addition, we evaluated the phenotypic changes, including initial biofilm formation, acid production and ATP turnover of S. mutans during heat stress. There were distinct patterns observed in the way that S. mutans responded to heat stress that included 66 transcription factors for the expression of functional genes being differentially expressed. Especially, response regulators of two component systems (TCSs), the repressors of heat shock proteins and regulators involved in sugar transporting and metabolism co-ordinated to enhance the cell’s survival and energy generation against heat stress in S. mutans.
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