scholarly journals Different Roles of EIIABMan and EIIGlc in Regulation of Energy Metabolism, Biofilm Development, and Competence in Streptococcus mutans

2006 ◽  
Vol 188 (11) ◽  
pp. 3748-3756 ◽  
Author(s):  
Jacqueline Abranches ◽  
Melissa M. Candella ◽  
Zezhang T. Wen ◽  
Henry V. Baker ◽  
Robert A. Burne
Keyword(s):  
Energy Metabolism ◽  
Streptococcus Mutans ◽  
Energy Levels ◽  
Sugar Metabolism ◽  
Oral Streptococci ◽  
Phosphotransferase System ◽  
Exogenous Dna ◽  
Biofilm Development ◽  
Metabolism Gene

ABSTRACT The phosphoenolpyruvate:sugar phosphotransferase system (PTS) is the major carbohydrate transport system in oral streptococci. The mannose-PTS of Streptococcus mutans, which transports mannose and glucose, is involved in carbon catabolite repression (CCR) and regulates the expression of known virulence genes. In this study, we investigated the role of EIIGlc and EIIABMan in sugar metabolism, gene regulation, biofilm formation, and competence. The results demonstrate that the inactivation of ptsG, encoding a putative EIIGlc, did not lead to major changes in sugar metabolism or affect the phenotypes of interest. However, the loss of EIIGlc was shown to have a significant impact on the proteome and to affect the expression of a known virulence factor, fructan hydrolase (fruA). JAM1, a mutant strain lacking EIIABMan, had an impaired capacity to form biofilms in the presence of glucose and displayed a decreased ability to be transformed with exogenous DNA. Also, the lactose- and cellobiose-PTSs were positively and negatively regulated by EIIABMan, respectively. Microarrays were used to investigate the profound phenotypic changes displayed by JAM1, revealing that EIIABMan of S. mutans has a key regulatory role in energy metabolism, possibly by sensing the energy levels of the cells or the carbohydrate availability and, in response, regulating the activity of transcription factors and carbohydrate transporters.

scholarly journals Coordinated Regulation of the EIIMan and fruRKI Operons of Streptococcus mutans by Global and Fructose-Specific Pathways

2017 ◽  
Vol 83 (21) ◽  
Author(s):  
Lin Zeng ◽  
Brinta Chakraborty ◽  
Tanaz Farivar ◽  
Robert A. Burne
Keyword(s):  
Energy Metabolism ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Regulation Of Gene Expression ◽  
Phosphotransferase System ◽  
Carbohydrate Source ◽  
Content Type ◽  
Fructose Metabolism ◽  
Biofilm Development

ABSTRACTThe glucose/mannose-phosphotransferase system (PTS) permease EIIManencoded bymanLMNin the dental caries pathogenStreptococcus mutanshas a dominant influence on sugar-specific, CcpA-independent catabolite repression (CR). Mutations inmanLaffect energy metabolism and virulence-associated traits, including biofilm formation, acid tolerance, and competence. Using promoter::reporter fusions, expression of themanLMNand thefruRKIoperons, encoding a transcriptional regulator, a fructose-1-phosphate kinase and a fructose-PTS permease EIIFru, respectively, was monitored in response to carbohydrate source and in mutants lacking CcpA, FruR, and components of EIIMan. Expression of genes for EIIManand EIIFruwas directly regulated by CcpA and CR, as evinced byin vivoandin vitromethods. Unexpectedly, not only was thefruRKIoperon negatively regulated by FruR, but also so wasmanLMN. Carbohydrate transport by EIIManhad a negative influence on expression ofmanLMNbut notfruRKI. In agreement with the proposed role of FruR in regulating these PTS operons, loss offruRorfruKsubstantially altered growth on a number of carbohydrates, including fructose. RNA deep sequencing revealed profound changes in gene regulation caused by deletion offruKorfruR. Collectively, these findings demonstrate intimate interconnection of the regulation of two major PTS permeases inS. mutansand reveal novel and important contributions of fructose metabolism to global regulation of gene expression.IMPORTANCEThe ability ofStreptococcus mutansand other streptococcal pathogens to survive and cause human diseases is directly dependent upon their capacity to metabolize a variety of carbohydrates, including glucose and fructose. Our research reveals that metabolism of fructose has broad influences on the regulation of utilization of glucose and other sugars, and mutants with changes in certain genes involved in fructose metabolism display profoundly different abilities to grow and express virulence-related traits. Mutants lacking the FruR regulator or a particular phosphofructokinase, FruK, display changes in expression of a large number of genes encoding transcriptional regulators, enzymes required for energy metabolism, biofilm development, biosynthetic and degradative processes, and tolerance of a spectrum of environmental stressors. Since fructose is a major component of the modern human diet, the results have substantial significance in the context of oral health and the development of dental caries.

scholarly journals Role of the Streptococcus mutans irvA Gene in GbpC-Independent, Dextran-Dependent Aggregation and Biofilm Formation

2009 ◽  
Vol 75 (22) ◽  
pp. 7037-7043 ◽  
Author(s):  
Min Zhu ◽  
Dragana Ajdić ◽  
Yuan Liu ◽  
David Lynch ◽  
Justin Merritt ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Growth Conditions ◽  
Parental Background ◽  
A Cell ◽  
Major Surface ◽  
Biofilm Development ◽  
Small Aggregation

ABSTRACT Dextran-dependent aggregation (DDAG) of Streptococcus mutans is an in vitro phenomenon that is believed to represent a property of the organism that is beneficial for sucrose-dependent biofilm development. GbpC, a cell surface glucan-binding protein, is responsible for DDAG in S. mutans when cultured under defined stressful conditions. Recent reports have described a putative transcriptional regulator gene, irvA, located just upstream of gbpC, that is normally repressed by the product of an adjacent gene, irvR. When repression of irvA is relieved, there is a resulting increase in the expression of GbpC and decreases in competence and synthesis of the antibiotic mutacin I. This study examined the role of irvA in DDAG and biofilm formation by engineering strains that overexpressed irvA (IrvA+) on an extrachromosomal plasmid. The IrvA+ strain displayed large aggregation particles that did not require stressful growth conditions. A novel finding was that overexpression of irvA in a gbpC mutant background retained a measure of DDAG, albeit very small aggregation particles. Biofilms formed by the IrvA+ strain in the parental background possessed larger-than-normal microcolonies. In a gbpC mutant background, the overexpression of irvA reversed the fragile biofilm phenotype normally associated with loss of GbpC. Real-time PCR and Northern blot analyses found that expression of gbpC did not change significantly in the IrvA+ strain but expression of spaP, encoding the major surface adhesin P1, increased significantly. Inactivation of spaP eliminated the small-particle DDAG. The results suggest that IrvA promotes DDAG not only by GbpC, but also via an increase in P1.

Phosphoenolpyruvate-Dependent Glucose Transport in Oral Streptococci

1973 ◽  
Vol 52 (6) ◽  
pp. 1209-1215 ◽  
Author(s):  
Charles F. Schachtele ◽  
John A. Mayo
Keyword(s):  
Glucose Uptake ◽  
Streptococcus Mutans ◽  
Glucose Transport ◽  
Enzyme System ◽  
Cell Suspensions ◽  
Oral Streptococci ◽  
Phosphotransferase System ◽  
Resting Cell

Streptococcus mutans, S sanguis, and S salivarius use a phosphoenolpyruvate (PEP)-dependent phosphotransferase system that results in phosphorylation of glucose at carbon 6. This enzyme system is not sensitive to fluoride. Glucose uptake into resting cell suspensions is sensitive to fluoride because of inhibition of intracellular PEP production. The glucose phosphotransferase system is constitutive in oral streptococci.

scholarly journals Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus mutans through Multiple Mechanisms

2016 ◽  
Vol 82 (12) ◽  
pp. 3671-3682 ◽  
Author(s):  
Lin Zeng ◽  
Tanaz Farivar ◽  
Robert A. Burne
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Sugar Metabolism ◽  
Amino Sugar ◽  
Amino Sugars ◽  
Mrna Levels ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Carbohydrate Source ◽  
Content Type

ABSTRACTBiochemical and genetic aspects of the metabolism of the amino sugarsN-acetylglucosamine (GlcNAc) and glucosamine (GlcN) by commensal oral streptococci and the effects of these sugars on interspecies competition with the dental caries pathogenStreptococcus mutanswere explored. MultipleS. mutanswild-type isolates displayed long lag phases when transferred from glucose-containing medium to medium with GlcNAc as the primary carbohydrate source, but commensal streptococci did not. Competition in liquid coculture or dual-species biofilms betweenS. mutansandStreptococcus gordoniishowed thatS. gordoniiwas particularly dominant when the primary carbohydrate was GlcN or GlcNAc. Transcriptional and enzymatic assays showed that the catabolic pathway for GlcNAc was less highly induced inS. mutansthan inS. gordonii. Exposure to H2O2, which is produced byS. gordoniiand antagonizes the growth ofS. mutans, led to reduced mRNA levels ofnagAandnagBinS. mutans. When the gene for the transcriptional regulatory NagR was deleted inS. gordonii, the strain produced constitutively high levels ofnagA(GlcNAc-6-P deacetylase),nagB(GlcN-6-P deaminase), andglmS(GlcN-6-P synthase) mRNA. Similar to NagR ofS. mutans(NagRSm), theS. gordoniiNagR protein (NagRSg) could bind to consensus binding sites (dre) in thenagA,nagB, andglmSpromoter regions ofS. gordonii. Notably, NagRSgbinding was inhibited by GlcN-6-P, but G-6-P had no effect, unlike for NagRSm. This study expands the understanding of amino sugar metabolism and NagR-dependent gene regulation in streptococci and highlights the potential for therapeutic applications of amino sugars to prevent dental caries.IMPORTANCEAmino sugars are abundant in the biosphere, so the relative efficiency of particular bacteria in a given microbiota to metabolize these sources of carbon and nitrogen might have a profound impact on the ecology of the community. Our investigation reveals that several oral commensal bacteria have a much greater capacity to utilize amino sugars than the dental pathogenStreptococcus mutansand that the ability of the model commensalStreptococcus gordoniito compete againstS. mutansis substantively enhanced by the presence of amino sugars commonly found in the oral cavity. The mechanisms underlying the greater capacity and competitive enhancements of the commensal are shown to depend on how the genes for the catabolic enzymes are regulated, the role of the allosteric modulators affecting such regulation, and the ability of amino sugars to enhance certain activities of the commensal that are antagonistic toS. mutans.

scholarly journals Structural and Molecular Basis of the Role of Starch and Sucrose in Streptococcus mutans Biofilm Development

2008 ◽  
Vol 75 (3) ◽  
pp. 837-841 ◽  
Author(s):  
M. I. Klein ◽  
S. Duarte ◽  
J. Xiao ◽  
S. Mitra ◽  
T. H. Foster ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Sugar Transport ◽  
Salivary Amylase ◽  
Pathogenic Potential ◽  
Expression Of Genes ◽  
Component Systems ◽  
Two Component Systems ◽  
Biofilm Development ◽  
Specific Sugar

ABSTRACT The interaction of sucrose and starch with bacterial glucosyltransferases and human salivary amylase may enhance the pathogenic potential of Streptococcus mutans within biofilms by influencing the structural organization of the extracellular matrix and modulating the expression of genes involved in exopolysaccharide synthesis and specific sugar transport and two-component systems.

scholarly journals Two Closely Related ABC Transporters in Streptococcus mutans Are Involved in Disaccharide and/or Oligosaccharide Uptake

2007 ◽  
Vol 190 (1) ◽  
pp. 168-178 ◽  
Author(s):  
Alexander J. Webb ◽  
Karen A. Homer ◽  
Arthur H. F. Hosie
Keyword(s):  
Streptococcus Mutans ◽  
Abc Transporters ◽  
Sole Carbon Source ◽  
Binding Protein ◽  
Sugar Metabolism ◽  
System Component ◽  
Phosphotransferase System ◽  
Atpase Subunits ◽  
Membrane Components ◽  
Distinct Membrane

ABSTRACT Streptococcus mutans has a large number of transporters apparently involved in the uptake of carbohydrates. At least two of these, the multiple sugar metabolism transporter, MsmEFGK, and the previously uncharacterized MalXFGK, are members of the ATP-binding cassette (ABC) superfamily. Mutation analysis revealed that the MsmEFGK and MalXFGK transporters are principally involved in the uptake of distinct disaccharides and/or oligosaccharides. Furthermore, the data also indicated an unusual protein interaction between the components of these two related transporters. Strains lacking msmE (which encodes a solute binding protein) can no longer utilize raffinose or stachyose but grow normally on maltodextrins in the absence of MalT, a previously characterized EIImal phosphotransferase system component. In contrast, a mutant of malX (which encodes a solute binding protein) cannot utilize maltodextrins but grows normally on raffinose or stachyose. Radioactive uptake assays confirmed that MalX, but not MsmE, is required for uptake of [U-14C]maltotriose and that MalXFGK is principally involved in the uptake of maltodextrins with as many as 7 glucose units. Surprisingly, inactivation of the corresponding ATPase components did not result in an equivalent abolition of growth: the malK mutant can grow on maltotetraose as a sole carbon source, and the msmK mutant can utilize raffinose. We propose that the ATPase domains of these ABC transporters can interact with either their own or the alternative transporter complex. Such unexpected interaction of ATPase subunits with distinct membrane components to form complete multiple ABC transporters may be widespread in bacteria.

scholarly journals Galactose Metabolism by Streptococcus mutans

2004 ◽  
Vol 70 (10) ◽  
pp. 6047-6052 ◽  
Author(s):  
Jacqueline Abranches ◽  
Yi-Ywan M. Chen ◽  
Robert A. Burne
Keyword(s):  
Streptococcus Mutans ◽  
Wild Type Strain ◽  
Sugar Metabolism ◽  
Growth Defect ◽  
Wild Type ◽  
Phosphotransferase System ◽  
Galactose Metabolism ◽  
Gene Encoding ◽  
Leloir Pathway ◽  
In The Wild

ABSTRACT The galK gene, encoding galactokinase of the Leloir pathway, was insertionally inactivated in Streptococcus mutans UA159. The galK knockout strain displayed only marginal growth on galactose, but growth on glucose or lactose was not affected. In strain UA159, the sugar phosphotransferase system (PTS) for lactose and the PTS for galactose were induced by growth in lactose and galactose, although galactose PTS activity was very low, suggesting that S. mutans does not have a galactose-specific PTS and that the lactose PTS may transport galactose, albeit poorly. To determine if the galactose growth defect of the galK mutant could be overcome by enhancing lactose PTS activity, the gene encoding a putative repressor of the operon for lactose PTS and phospho-β-galactosidase, lacR, was insertionally inactivated. A galK and lacR mutant still could not grow on galactose, although the strain had constitutively elevated lactose PTS activity. The glucose PTS activity of lacR mutants grown in glucose was lower than in the wild-type strain, revealing an influence of LacR or the lactose PTS on the regulation of the glucose PTS. Mutation of the lacA gene of the tagatose pathway caused impaired growth in lactose and galactose, suggesting that galactose can only be efficiently utilized when both the Leloir and tagatose pathways are functional. A mutation of the permease in the multiple sugar metabolism operon did not affect growth on galactose. Thus, the galactose permease of S. mutans is not present in the gal, lac, or msm operons.

scholarly journals Disruption of Streptococcus mutans and Candida albicans synergy by a commensal streptococcus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Joshua T. Huffines ◽  
Jessica A. Scoffield
Keyword(s):  
Candida Albicans ◽  
Streptococcus Mutans ◽  
Dental Plaque ◽  
Early Childhood Caries ◽  
Sugar Metabolism ◽  
Independent Manner ◽  
Biofilm Model ◽  
Carious Lesions ◽  
Biofilm Development ◽  
The Impact

AbstractPolymicrobial interactions in dental plaque play a significant role in dysbiosis and homeostasis in the oral cavity. In early childhood caries, Streptococcus mutans and Candida albicans are often co-isolated from carious lesions and associated with increased disease severity. Studies have demonstrated that metabolic and glucan-dependent synergism between C. albicans and S. mutans contribute to enhanced pathogenesis. However, it is unclear how oral commensals influence pathogen synergy. Streptococcus parasanguinis, a hydrogen peroxide (H2O2) producing oral commensal, has antimicrobial activity against S. mutans. In this study, we utilized a three species biofilm model to understand the impact of S. parasanguinis on S. mutans and C. albicans synergy. We report that S. parasanguinis disrupts S. mutans and C. albicans biofilm synergy in a contact and H2O2-independent manner. Further, metabolomics analysis revealed a S. parasanguinis-driven alteration in sugar metabolism that restricts biofilm development by S. mutans. Moreover, S. parasanguinis inhibits S. mutans glucosyltransferase (GtfB) activity, which is important for glucan matrix development and GtfB-mediated binding to C. albicans mannan. Taken together, our study describes a new antimicrobial role for S. parasanguinis and highlights how this abundant oral commensal may be utilized to attenuate pathogen synergism.

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