Gene expression and metabolic activity of Streptococcus mutans during exposure to dietary carbohydrates glucose, sucrose, lactose and xylitol
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ABSTRACT:
ORGANISM(S): Streptococcus mutans
PROVIDER: GSE207392 | GEO | 2023/12/18
REPOSITORIES: GEO
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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.
2017-05-20 | GSE98020 | GEO
Project description:Oral streptococci metabolize carbohydrate to produce organic acids, not only decrease the environmental pH, but also increase osmolality of dental plaque fluid due to tooth demineralization and consequent calcium and phosphate accumulation. Thus, to persevere in the dental plaque, acidogenic bacteria should evolve sophisticated molecular machineries to counter the detrimental effect of elevated osmolality. This study was aimed to obtain a global view on strategies taken by streptococcus mutans to deal with physiologically relevant elevated osmolality, and preserves within a cariogenic dental plaque. We investigated phenotypic change of S. mutans biofilm upon sub-lethal level of hyperosmotic challenge. We found that hyperosmotic condition was able to initiate S. mutans biofilm dispersal by reducing both microbial content and extracellular polysaccharides matrix. We then used DNA microarray with qPCR validation to systemically investigate the underlying molecular machinery of this bacteria in response to hyperosmotic stimuli. Among those identified 50 differentially regulated genes, down-regulation of gtfB and comC were believed to be responsible for the observed biofilm dispersal. Further analysis of microarray data showed significant up-regulation of genes and pathways involved in carbohydrates metabolism. Specific genes involved in heat shock response and acid tolerance were also upregulated, indicating potential cross-talk between hyperosmotic and other environmental stress. Based on the data obtained in this study, we believe that although hyperosmotic condition may induce significant stress response on S. mutans, this cariogenic bacterium has evolved sophisticated molecular machineries to counter those elicited detrimental effects. In the meantime, it will take full advantage of these environmental stimuli to better fit the fluctuating environments within oral cavity, and thus emerge as numeric-predominant bacteria under cariogenic conditions. A six-chip study using total RNA recovered from mid-logarithmic phase of S. mutans UA159 from three separate cultures of strains submitted for 15 minutes to hyperosmotic stimuli (0.4M NaCl) and three separate cultures of strains kept under no stress condition.
2013-08-31 | E-GEOD-47170 | biostudies-arrayexpress
Project description:Background. Hematopoietic cell transplantation (HCT) is a potentially curative therapy for a wide range of pediatric malignant and nonmalignant diseases. However, complications, including blood stream infection (BSI) remain a major cause of morbidity and mortality. While certain bacteria that are abundant in the oral microbiome, such as S. mitis, can cause BSI, the role of the oral microbial community in the etiology of BSI is not well understood. The finding that the use of xylitol wipes, which specifically targets the cariogenic bacteria S. mutans is associated with reduced BSI in pediatric patients, lead us to investigate dental caries as a risk factor for BSI. Methods. A total of 41 pediatric patients admitted for allogenic or autologous HCT, age 8 months to 25 years, were enrolled. Subjects with high dental caries risk were identified as those who had dental restorations completed within 2 months of admission for transplant, or who had untreated decay. Fisher’s exact test was used to determine if there was a significant association between caries risk and BSI. Dental plaque and saliva were collected on a cotton swab from a subset of 4 high caries risk (HCR) and 4 low caries risk (LCR) children following pretransplant conditioning. 16SrRNA sequencing was used to compare the microbiome of HCR and LCR subjects and to identify microbes that were significantly different between the 2 groups. Results. There was a statistically significant association between caries risk and BSI (p<0.035) (Fisher’s exact test). Multivariate logistic regression analysis showed children in the high dental caries risk group were 21.39 times more likely to have BSI, with no significant effect of age or mucositis severity. HCR subjects showed significantly reduced microbial alpha diversity as compared to LCR subjects. LEfse metagenomic analyses, showed the oral microbiome in HCR children enriched in order Lactobacillales. This order includes Streptococcus and Lactobacillus, both which contain bacteria primarily associated with dental caries. Discussion. These findings support the possibility that the cariogenic microbiome can enhance the risk of BSI in pediatric populations. Future metagenomic analyses to measure microbial differences at, before, and after conditioning related to caries risk, may further unravel the complex relationship between the oral microbiome, and whether it affects health outcomes such as BSI.
2022-04-05 | GSE199991 | GEO
Project description:Streptococcus mutans, the primary etiologic agent of human dental caries, and a variety of oral Streptococcus and Actinomyces spp. synthesize high molecular mass homopolymers of fructose (fructans) with predominantly β2,1- (inulins) or β2,6-linkages (levans). The ability of S. mutans to degrade fructans contributes to the severity of dental caries. The extracellular product of fruA of S. mutans is an exo-β-D-fructofuranosidase that releases fructose from levan and inulin. Located 70 bp downstream of fruA, fruB encodes a member of the glycoside hydrolase family 32, but the function of FruB has not been established.In this study, the transcriptomic analysis of UA159 and a fruB mutant grown on 0.2% levan revealed differential expression of genes encoding ABC transporters, transcriptional regulators and genes involved in growth and stress tolerance. The results provide new insights into the mechanisms of action by which FruB utilizes homo-polymers of fructose, specifically levan. The findings significantly enhance our understanding of the genetics and physiology of this cariogenic pathogen S. mutans.
2022-04-15 | GSE200727 | GEO
Project description:Astronauts have been previously shown to exhibit decreased salivary lysozyme and increased dental calculus and gingival inflammation in response to space flight, host factors that could contribute to oral diseases such as caries and periodontitis. However, the specific physiological response of caries-causing bacteria such as Streptococcus mutans to space flight and/or ground-based simulated microgravity has not been extensively investigated. In this study, High Aspect Ratio Vessel (HARV) S. mutans simulated microgravity and normal gravity cultures were assessed for changes in metabolite and transcriptome profiles, H2O2 resistance, and competence in sucrose-containing biofilm media. Stationary phase S. mutans simulated microgravity cultures displayed increased killing by H2O2 compared to normal gravity control cultures, but competence was not affected. RNA-seq analysis revealed that expression of 153 genes was up-regulated ≥ 2-fold and 94 genes down-regulated ≥ 2-fold during simulated microgravity HARV growth. These included a number of genes located on extrachromosomal elements, as well as genes involved in carbohydrate metabolism, translation, and stress responses. Collectively, these results suggest that growth under microgravity analog conditions promotes changes in S. mutans gene expression and physiology that may translate to an altered cariogenic potential of this organism during space flight missions.
2017-03-01 | GSE90166 | GEO
Project description:For Streptococcus mutans, the major etiologic agent of human dental caries, sucrose is the carbohydrate that contributes in the most significant manner to establishment, persistence and virulence of the organism. However, because this organism produces multiple extracellular sucrolytic enzymes that can release hexoses from sucrose, it has not been possible to study the specific effects of sucrose transport and metabolism on gene expression in the absence of carbohydrates that by themselves can elicit catabolite repression and induce expression of multiple genes. Employing RNA deep sequencing (RNA-Seq) technology and mutants that lacked particular sucrose-metabolizing enzymes, we compared the transcriptomes of S. mutans growing on glucose, fructose or sucrose as the sole carbohydrate. The results provide a variety of new insights into the impact of sucrose transport and metabolism by S. mutans, including the likely expulsion of fructose after sucrose internalization and hydrolysis, and identified a set of genes that are differentially regulated by sucrose versus fructose. The findings significantly enhance our understanding of the genetics and physiology of this cariogenic pathogen.
2015-11-12 | GSE74939 | GEO
Project description:The lesions of enamel caries can be considered as the outcome of dysbiotic changes in the biofilm community of supragingival dental plaque. Demineralization occurs as the cumulative outcome of repeated shifts towards a less diverse microbiota that produces and tolerates a low pH environment in tooth sites that are sheltered from protective factors in host saliva. Although the etiology of caries is multifactorial, frequent consumption of foods rich in fermentable carbohydrates, notably sucrose, appears to be one of the major factors driving the microbiota in the direction of dysbiosis, particularly in the case of otherwise healthy children with normal salivary flow. Streptococcus mutans and closely related species (such as Streptococcus sobrinus) have long been considered to play a primary etiological role in dental caries. S. mutans responds to sucrose by producing large quantities of lactic acid. It is very tolerant of low pH, and produces an insoluble extracellular polysaccharide that may sequester acid at tooth surfaces. The mechanisms behind those putative virulence factors have been intensively studied in monoculture, and recently in simple multi-species consortia. Much less is known of other species that may also contribute to or protect against dysbiosis driven by dietary carbohydrates. Some strains of “non-mutans” streptococci produce and tolerate acid at levels comparable to S. mutans, while others show increased ariginolytic capabilities, which may act to raise pH within the biofilm matrix. S. mutans tends to be a minority species even in caries-active children, and carious lesions likewise can occur in children with no detectable S. mutans. 16S rDNA-based metagenomic comparisons of caries-active and caries-free subjects have detected associations between caries and a variety of oral species, including not only non-mutans streptococci, but also members of other genera, such as Scardovia and Bifidobacterium. Caries associations have not been consistent between studies. Moreover, different taxonomic clusters have been defined as subgroups within the same study. This raises an important point. Although caries-associated communities are typically less diverse than healthy supragingival plaque overall, those dysbiotic communities still display considerable taxonomic diversity between affected individuals. That in turn raises the question of whether it is desirable to define biomarkers of dysbiosis that are less dependent on taxonomy. The Human Microbiome project generated comprehensive metagenomic data for a wide variety of body sites in healthy subjects, including supragingival plaque. Although most of that data was based on 16S rDNA sequencing, shotgun metagenomics was also used to catalog the functional potential of all microbial genes within a smaller subset of subjects. One of the key findings was that healthy sites from different people were broadly similar with respect to their functional profiles, even though there was extensive individual variation in their taxonomic profiles. It is possible that the “conservation of function” concept may also extend to dysbiotic communities. This would explain why microbial communities associated with caries still show considerable taxonomic variation. In that case, differential patterns of community-wide gene and/or protein expression might provide a more accurate indicator of dysbiosis than can be achieved by counting caries-associated species. Metatranscriptomic or metaproteomic approaches can be used to provide information on function. A recent metatranscriptomic comparison of subgingival plaque from healthy and periodontally diseased sites in three subjects has provided data that support the “conservation of function” concept. They observed that taxonomically diverse diseased sites shared conserved gene expression profiles [20]. By the same token, a recent metaproteomic comparison of gut microbiotas from healthy controls to Crohn’s disease patients found that major shifts in protein expression by function did not always correlate with changes in taxon relative abundance [21]. In this metaproteomic study, we found that sucrose–induced changes in protein expression patterns for pathways involving glycolysis, lactate production, aciduricity and ammonia/glutamate metabolism were likewise conserved in taxonomically diverse dysbiotic oral microcosm biofilm communities.
2016-01-04 | PXD003151 | Pride
Project description:Lysine malonylation is an evolutionarily conserved PTM from bacteria to mammals and involves malonyl-coenzyme (CoA) as a cofactor. Since the malonyl group has an acidic carboxylic group under physiological pH, malonylated lysine is negatively charged, which might impact on protein function and enzymatic activities. Like other short-chain acyl-CoAs, malonyl-CoA can be synthesized from its corresponding short-chain acyl salt, malonate, catalyzed by malonyl-CoA synthetase (Witkowski et al., 2011). In addition, malonyl-CoA can be produced during the carboxylation of acetyl-CoA by acetyl-CoA carboxylase (ACC), the carboxylation of acetyl-CoA by propionyl-CoA carboxylase, and the β-oxidation of old-chain-length dicarboxylic acids (Peng et al., 2011). Most studies on Kmal have been performed in mammalian systems and identified thousands of malonylated sites, revealing its role in the progress of diseases like type 2 diabetes, schizophrenia, and cardiac hypertrophy (Du et al., 2015; Smith et al., 2022; Wu et al., 2022). There has been increasing interest in dissecting the regulatory roles of Kmal in several bacterial species, such as Escherichia coli (Qian et al., 2016), Bacillus amyloliquefaciens (Fan et al., 2017), Mycobacterium tuberculosis (Bi et al., 2022), and Staphylococcus aureus (Shi et al., 2021), which demonstrates that Kmal exists in diverse prokaryotic organisms and participates in the regulation of various physiological processes. Even so, whether Kmal exists and affects protein functions in streptococci remains unknown. S. mutans is considered to be the most prevalent and cariogenic species in active carious lesions of humans, residing primarily in dental plaque, which is a biofilm that forms on the tooth surfaces. During the past decades, studies of S. mutans have focused on revealing the molecular mechanisms underlying the robust biofilm formation on tooth surfaces, the metabolism of a wide variety of carbohydrates obtained from the host diet, and the adaption of numerous environmental challenges (Lemos et al., 2019). Several studies have been performed to reveal the roles of PTMs in biofilm and cariogenic virulence. Wang et al. found that the phosphorylation of VicR could inhibit the expression of the glucosyltransferases gtfBC, thereby reducing the synthesis of extracellular polysaccharides (EPS), the major component of cariogenic biofilm (Wang et al., 2021). Acetylome study on the S. mutans depicted that acetylated substrates were globally altered in the biofilm state compared to the planktonic state, and the acetylated GtfBC showed decreased activities (Lei et al., 2021; Ma et al., 2021). Our previous study revealed that the S-glutathionylation of a thioredoxin-like protein is important for interspecies competition and cariogenicity of S. mutans(Li et al., 2020). These results suggest that various PTM types exist in S. mutans and participate in diverse physiological processes. The genome of S. mutans UA159 codes an acetyl coenzyme A carboxylase (ACC), which could synthesize malonyl-CoA through the carboxylation of acetyl-CoA (Ajdić et al., 2002), implying the existence of malonylation in this bacterium. Therefore, this study aimed to confirm the existence of Kmal in S. mutans and identify the malonylated sites globally. The present findings provide a systematic view of the functional roles of Kmal in various metabolic pathways of S. mutans.
2022-11-17 | PXD038045 | Pride
Project description:Oral streptococci metabolize carbohydrate to produce organic acids, which not only decrease the environmental pH, but also increase osmolality of dental plaque fluid due to tooth demineralization and consequent calcium and phosphate accumulation. Despite these unfavorable environmental changes, the bacteria continue to thrive. The aim of this study was to obtain a global view on strategies taken by Streptococcus mutans to deal with physiologically relevant elevated osmolality, and perseveres within a cariogenic dental plaque. We investigated phenotypic change of S. mutans biofilm upon hyperosmotic challenge. We found that the hyperosmotic condition was able to initiate S. mutans biofilm dispersal by reducing both microbial content and extracellular polysaccharides matrix. We then used whole-genome microarray with quantitative RT-PCR validation to systemically investigate the underlying molecular machineries of this bacterium in response to the hyperosmotic stimuli. Among those identified 40 deferentially regulated genes, down-regulation of gtfB and comC were believed to be responsible for the observed biofilm dispersal. Further analysis of microarray data showed significant up-regulation of genes and pathways involved in carbohydrate metabolism. Specific genes involved in heat shock response and acid tolerance were also upregulated, indicating potential cross-talk between hyperosmotic and other environmental stress. Hyperosmotic condition induces significant stress response on S. mutans at both phenotypic and transcriptomic levels. In the meantime, it may take full advantage of these environmental stimuli to better fit the fluctuating environments within oral cavity, and thus emerges as numeric-predominant bacterium under cariogenic conditions.
2013-08-31 | GSE47170 | GEO
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.
2014-10-01 | GSE59302 | GEO