scholarly journals Interactions between Oral Bacteria: Inhibition of Streptococcus mutans Bacteriocin Production by Streptococcus gordonii

2005 ◽  
Vol 71 (1) ◽  
pp. 354-362 ◽  
Author(s):  
Bing-Yan Wang ◽  
Howard K. Kuramitsu
Keyword(s):  
Quorum Sensing ◽  
Streptococcus Mutans ◽  
Parent Strain ◽  
Oral Bacteria ◽  
Bacteriocin Production ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Signaling System ◽  
Signaling Systems ◽  
Bacteria Inhibition

ABSTRACT Streptococcus mutans has been recognized as an important etiological agent in human dental caries. Some strains of S. mutans also produce bacteriocins. In this study, we sought to demonstrate that bacteriocin production by S. mutans strains GS5 and BM71 was mediated by quorum sensing, which is dependent on a competence-stimulating peptide (CSP) signaling system encoded by the com genes. We also demonstrated that interactions with some other oral streptococci interfered with S. mutans bacteriocin production both in broth and in biofilms. The inhibition of S. mutans bacteriocin production by oral bacteria was stronger in biofilms than in broth. Using transposon Tn916 mutagenesis, we identified a gene (sgc; named for Streptococcus gordonii challisin) responsible for the inhibition of S. mutans bacteriocin production by S. gordonii Challis. Interruption of the sgc gene in S. gordonii Challis resulted in attenuated inhibition of S. mutans bacteriocin production. The supernatant fluids from the sgc mutant did not inactivate the exogenous S. mutans CSP as did those from the parent strain Challis. S. gordonii Challis did not inactivate bacteriocin produced by S. mutans GS5. Because S. mutans uses quorum sensing to regulate virulence, strategies designed to interfere with these signaling systems may have broad applicability for biological control of this caries-causing organism.

scholarly journals Amino Sugars Reshape Interactions between Streptococcus mutans and Streptococcus gordonii

2020 ◽  
Vol 87 (1) ◽  
Author(s):  
Lulu Chen ◽  
Alejandro R. Walker ◽  
Robert A. Burne ◽  
Lin Zeng
Keyword(s):  
Gene Expression ◽  
Streptococcus Mutans ◽  
Single Species ◽  
Oral Bacteria ◽  
Amino Sugars ◽  
Sequencing Analysis ◽  
Streptococcus Gordonii ◽  
Bacterial Gene ◽  
Content Type ◽  
The Impact

ABSTRACT Amino sugars, particularly glucosamine (GlcN) and N-acetylglucosamine (GlcNAc), are abundant carbon and nitrogen sources supplied in host secretions and in the diet to the biofilms colonizing the human oral cavity. Evidence is emerging that these amino sugars provide ecological advantages to beneficial commensals over oral pathogens and pathobionts. Here, we performed transcriptome analysis on Streptococcus mutans and Streptococcus gordonii growing in single-species or dual-species cultures with glucose, GlcN, or GlcNAc as the primary carbohydrate source. Compared to glucose, GlcN caused drastic transcriptomic shifts in each species of bacteria when it was cultured alone. Likewise, cocultivation in the presence of GlcN yielded transcriptomic profiles that were dramatically different from the single-species results from GlcN-grown cells. In contrast, GlcNAc elicited only minor changes in the transcriptome of either organism in single- and dual-species cultures. Interestingly, genes involved in pyruvate metabolism were among the most significantly affected by GlcN in both species, and these changes were consistent with measurements of pyruvate in culture supernatants. Differing from what was found in a previous report, growth of S. mutans alone with GlcN inhibited the expression of multiple operons required for mutacin production. Cocultivation with S. gordonii consistently increased the expression of two manganese transporter operons (slo and mntH) and decreased expression of mutacin genes in S. mutans. Conversely, S. gordonii appeared to be less affected by the presence of S. mutans but did show increases in genes for biosynthetic processes in the cocultures. In conclusion, amino sugars profoundly alter the interactions between pathogenic and commensal streptococci by reprogramming central metabolism. IMPORTANCE Carbohydrate metabolism is central to the development of dental caries. A variety of sugars available to dental microorganisms influence the development of caries by affecting the physiology, ecology, and pathogenic potential of tooth biofilms. Using two well-characterized oral bacteria, one pathogen (Streptococcus mutans) and one commensal (Streptococcus gordonii), in an RNA deep-sequencing analysis, we studied the impact of two abundant amino sugars on bacterial gene expression and interspecies interactions. The results indicated large-scale remodeling of gene expression induced by GlcN in particular, affecting bacterial energy generation, acid production, protein synthesis, and release of antimicrobial molecules. Our study provides novel insights into how amino sugars modify bacterial behavior, information that will be valuable in the design of new technologies to detect and prevent oral infectious diseases.

scholarly journals Streptococcal Antagonism in Oral Biofilms: Streptococcus sanguinis and Streptococcus gordonii Interference with Streptococcus mutans

2008 ◽  
Vol 190 (13) ◽  
pp. 4632-4640 ◽  
Author(s):  
Jens Kreth ◽  
Yongshu Zhang ◽  
Mark C. Herzberg
Keyword(s):  
Streptococcus Mutans ◽  
Bacterial Species ◽  
Ecological Factors ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Interspecies Interactions ◽  
Streptococcus Sanguinis ◽  
Production Of Hydrogen ◽  
Oral Biofilms ◽  
Competence System

ABSTRACT Biofilms are polymicrobial, with diverse bacterial species competing for limited space and nutrients. Under healthy conditions, the different species in biofilms maintain an ecological balance. This balance can be disturbed by environmental factors and interspecies interactions. These perturbations can enable dominant growth of certain species, leading to disease. To model clinically relevant interspecies antagonism, we studied three well-characterized and closely related oral species, Streptococcus gordonii, Streptococcus sanguinis, and cariogenic Streptococcus mutans. S. sanguinis and S. gordonii used oxygen availability and the differential production of hydrogen peroxide (H2O2) to compete effectively against S. mutans. Interspecies antagonism was influenced by glucose with reduced production of H2O2. Furthermore, aerobic conditions stimulated the competence system and the expression of the bacteriocin mutacin IV of S. mutans, as well as the H2O2-dependent release of heterologous DNA from mixed cultures of S. sanguinis and S. gordonii. These data provide new insights into ecological factors that determine the outcome of competition between pioneer colonizing oral streptococci and the survival mechanisms of S. mutans in the oral biofilm.

scholarly journals Genetic Analysis of Mutacin B-Ny266, a Lantibiotic Active against Caries Pathogens

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
Delphine Dufour ◽  
Abdelahhad Barbour ◽  
Yuki Chan ◽  
Marcus Cheng ◽  
Taimoor Rahman ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Dental Plaque ◽  
Oral Bacteria ◽  
Oral Streptococci ◽  
Chromosomal Locus ◽  
Content Type ◽  
Genes Encoding ◽  
Plaque Biofilm

ABSTRACT Bacteriocins are ribosomally synthesized proteinaceous antibacterial peptides. They selectively interfere with the growth of other bacteria. The production and secretion of bacteriocins confer a distinct ecological advantage to the producer in competing against other bacteria that are present in the same ecological niche. Streptococcus mutans, a significant contributor to the development of dental caries, is one of the most prolific producers of bacteriocins, known as mutacins in S. mutans. In this study, we characterized the locus encoding mutacin B-Ny266, a lantibiotic with a broad spectrum of activity. The chromosomal locus is composed of six predicted operon structures encoding proteins involved in regulation, antimicrobial activity, biosynthesis, modification, transport, and immunity. Mutacin B-Ny266 was purified from semisolid cultures, and two inhibitory peptides, LanA and LanA′, were detected. Both peptides were highly modified. Such modifications include dehydration of serine and threonine and the formation of a C-terminal aminovinyl-cysteine (AviCys) ring. While LanA peptide alone is absolutely required for antimicrobial activity, the presence of LanA′ enhanced the activity of LanA, suggesting that B-Ny266 may function as a two-peptide lantibiotic. The activation of lanAA′ expression is most likely controlled by the conserved two-component system NsrRS, which is activated by LanA peptide but not by LanA′. The chromosomal locus encoding mutacin B-Ny266 was not universally conserved in all sequenced S. mutans genomes. Intriguingly, the genes encoding LanAA′ peptides were restricted to the most invasive serotypes of S. mutans. IMPORTANCE Although dental caries is largely preventable, it remains the most common and costly infectious disease worldwide. Caries is initiated by the presence of dental plaque biofilm that contains Streptococcus mutans, a species extensively characterized by its role in caries development and formation. S. mutans deploys an arsenal of strategies to establish itself within the oral cavity. One of them is the production of bacteriocins that confer a competitive advantage by targeting and killing closely related competitors. In this work, we found that mutacin B-Ny266 is a potent lantibiotic that is effective at killing a wide array of oral streptococci, including nearly all S. mutans strains tested. Lantibiotics produced by oral bacteria could represent a promising strategy to target caries pathogens embedded in dental plaque biofilm.

scholarly journals Regulation of Bacteriocin Production and Cell Death by the VicRK Signaling System in Streptococcus mutans

2012 ◽  
Vol 194 (6) ◽  
pp. 1307-1316 ◽  
Author(s):  
D. B. Senadheera ◽  
M. Cordova ◽  
E. A. Ayala ◽  
L. E. Chavez de Paz ◽  
K. Singh ◽  
...  
Keyword(s):  
Cell Death ◽  
Streptococcus Mutans ◽  
Bacteriocin Production ◽  
Signaling System

scholarly journals Amino Sugars Modify Antagonistic Interactions between Commensal Oral Streptococci andStreptococcus mutans

2019 ◽  
Author(s):  
Lulu Chen ◽  
Brinta Chakraborty ◽  
Jing Zou ◽  
Robert A. Burne ◽  
Lin Zeng
Keyword(s):  
Streptococcus Mutans ◽  
Ex Vivo ◽  
Arginine Deiminase ◽  
Clinical Isolates ◽  
Amino Sugars ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Oral Biofilms ◽  
Low Passage

ABSTRACTN-acetylglucosamine (GlcNAc) and glucosamine (GlcN) enhance the competitiveness of the laboratory strain DL1 ofStreptococcus gordoniiagainst the caries pathogenStreptococcus mutans. Here we examine how amino sugars affect the interaction of five low-passage clinical isolates of abundant commensal streptococci withS. mutansutilizing a dual-species biofilm model. Compared to glucose, growth on GlcN or GlcNAc significantly reduced the viability ofS. mutansin co-cultures with most commensals, shifting the proportions of species. Consistent with these results, production of H2O2was increased in most commensals when growing on amino sugars, and inhibition ofS. mutansbyStreptococcus cristatus, Streptococcus oralis,orS. gordoniiwas enhanced by amino sugars on agar plates. All commensals exceptS. oralishad higher arginine deiminase activities when grown on GlcN, and in some cases GlcNAc. Inex vivobiofilms formed using pooled cell-containing saliva (CCS), the proportions ofS. mutanswere drastically diminished when GlcNAc was the primary carbohydrate. Increased production of H2O2could account in large part for the inhibitory effects of CCS biofilms. Surprisingly, amino sugars appeared to improve mutacin production byS. mutanson agar plates, suggesting that the commensals have mechanisms to actively subvert antagonism byS. mutansin co-cultures. Collectively, these findings demonstrate that amino sugars can enhance the beneficial properties of low-passage commensal oral streptococci and highlight their potential for moderating the cariogenicity of oral biofilms.SIGNIFICANCEDental caries is driven by dysbiosis of oral biofilms in which dominance by acid-producing and acid-tolerant bacteria results in loss of tooth mineral. Our previous work demonstrated the beneficial effects of amino sugars, GlcNAc and GlcN, in promoting the antagonistic properties of a health-associated oral bacterium,Streptococcus gordonii,in competition with the major caries pathogenStreptococcus mutans.Here we investigated 5 low-passage clinical isolates of the most common streptococcal species to establish how amino sugars may influence the ecology and virulence of oral biofilms. Using multiplein vitromodels, including a human saliva-derived microcosm biofilm, experiments showed significant enhancement by at least one amino sugar in the ability of most of these bacteria to suppress the caries pathogen. Therefore, our findings demonstrated the mechanism of action by which amino sugars may affect human oral biofilms to promote health.

scholarly journals Transcriptomic Responses to Coaggregation between Streptococcus gordonii and Streptococcus oralis

2021 ◽  
Author(s):  
Siew Woh Choo ◽  
Waleed K. Mohammed ◽  
Naresh V. R. Mutha ◽  
Nadia Rostami ◽  
Halah Ahmed ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Oral Health ◽  
Dental Plaque ◽  
Oral Bacteria ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Streptococcus Oralis ◽  
Wide Range ◽  
Key Genes ◽  
Biofilm Development

Cell-cell adhesion between oral bacteria plays a key role in the development of polymicrobial communities such as dental plaque. Oral streptococci such as Streptococcus gordonii and Streptococcus oralis are important early colonizers of dental plaque and bind to a wide range of different oral microorganisms, forming multispecies clumps or ‘coaggregates’. S. gordonii actively responds to coaggregation by regulating gene expression. To further understand these responses, we assessed gene regulation in S. gordonii and S. oralis following coaggregation in 25% human saliva. Coaggregates were formed by mixing and, after 30 minutes, RNA was extracted for Dual RNASeq analysis. In S. oralis , 18 genes (6 upregulated and 12 downregulated) were regulated by coaggregation. Significantly downregulated genes encoded functions such as amino acid and antibiotic biosynthesis, ribosome and central carbon metabolism. In total, 28 genes were differentially regulated in Streptococcus gordonii (25 upregulated and 3 downregulated). Many genes associated with transporters and a two component (NisK/SpaK) regulatory system were upregulated following coaggregation. Our comparative analyses of S. gordonii - S. oralis with different previously published S. gordonii pairings ( S. gordonii - Fusobacterium nucleatum and S. gordonii - Veillonella parvula ) suggest that the gene regulation is specific to each pairing and responses do not appear to be conserved. This ability to distinguish between neighboring bacteria may be important for S. gordonii to adapt appropriately during the development of complex biofilms such as dental plaque. Importance Dental plaque is responsible for two of the most prevalent diseases in humans, dental caries and periodontitis. Controlling the formation of dental plaque and preventing the transition from oral health to disease requires a detailed understanding of microbial colonization and biofilm development. Streptococci are among the most common colonizers of dental plaque. This study identifies key genes that are regulated when oral streptococci bind to one another, as they do in the early stages of dental plaque formation. We show that specific genes are regulated in two different oral streptococci following the formation of mixed-species aggregates. The specific responses of S. gordonii to coaggregation with S. oralis are different from coaggregation with other oral bacteria. Targeting the key genes that are upregulated during interspecies interactions may be a powerful approach to control the developing biofilm and maintain oral health.

scholarly journals Amino Sugars Modify Antagonistic Interactions between Commensal Oral Streptococci andStreptococcus mutans

2019 ◽  
Vol 85 (10) ◽  
Author(s):  
Lulu Chen ◽  
Brinta Chakraborty ◽  
Jing Zou ◽  
Robert A. Burne ◽  
Lin Zeng
Keyword(s):  
Streptococcus Mutans ◽  
Arginine Deiminase ◽  
Clinical Isolates ◽  
Amino Sugars ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Content Type ◽  
Oral Biofilms ◽  
Passage Number ◽  
Low Passage

ABSTRACTN-Acetylglucosamine (GlcNAc) and glucosamine (GlcN) enhance the competitiveness of the laboratory strain DL1 ofStreptococcus gordoniiagainst the caries pathogenStreptococcus mutans. Here, we examine how amino sugars affect the interaction of five low-passage-number clinical isolates of abundant commensal streptococci withS. mutansby utilizing a dual-species biofilm model. Compared to that for glucose, growth on GlcN or GlcNAc significantly reduced the viability ofS. mutansin cocultures with most commensals, shifting the proportions of species. Consistent with these results, production of H2O2was increased in most commensals when growing on amino sugars, and inhibition ofS. mutansbyStreptococcus cristatus,Streptococcus oralis, orS. gordoniiwas enhanced by amino sugars on agar plates. All commensals exceptS. oralishad higher arginine deiminase activities when grown on GlcN and, in some cases, GlcNAc. Inex vivobiofilms formed using pooled cell-containing saliva (CCS), the proportions ofS. mutanswere drastically diminished when GlcNAc was the primary carbohydrate. Increased production of H2O2could account in large part for the inhibitory effects of CCS biofilms. Surprisingly, amino sugars appeared to improve mutacin production byS. mutanson agar plates, suggesting that the commensals have mechanisms to actively subvert antagonism byS. mutansin cocultures. Collectively, these findings demonstrate that amino sugars can enhance the beneficial properties of low-passage-number commensal oral streptococci and highlight their potential for moderating the cariogenicity of oral biofilms.IMPORTANCEDental caries is driven by dysbiosis of oral biofilms in which dominance by acid-producing and acid-tolerant bacteria results in loss of tooth mineral. Our previous work demonstrated the beneficial effects of amino sugars GlcNAc and GlcN in promoting the antagonistic properties of a health-associated oral bacterium,Streptococcus gordonii, in competition with the major caries pathogenStreptococcus mutans. Here, we investigated 5 low-passage-number clinical isolates of the most common streptococcal species to establish how amino sugars may influence the ecology and virulence of oral biofilms. Using multiplein vitromodels, including a human saliva-derived microcosm biofilm, experiments showed significant enhancement by at least one amino sugar in the ability of most of these bacteria to suppress the caries pathogen. Therefore, our findings demonstrated the mechanism of action by which amino sugars may affect human oral biofilms to promote health.

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 Amino Sugars Reshape Interactions between Streptococcus mutans and Streptococcus gordonii

2020 ◽  
Author(s):  
Lulu Chen ◽  
Alejandro R. Walker ◽  
Robert A. Burne ◽  
Lin Zeng
Keyword(s):  
Gene Expression ◽  
Streptococcus Mutans ◽  
Single Species ◽  
Oral Bacteria ◽  
Amino Sugars ◽  
Sequencing Analysis ◽  
Streptococcus Gordonii ◽  
Pathogenic Potential ◽  
Bacterial Gene ◽  
The Impact

ABSTRACTAmino sugars, particularly glucosamine (GlcN) and N-acetylglucosamine (GlcNAc), are abundant carbon and nitrogen sources that are continually supplied in host secretions and in the diet to the biofilms colonizing the human oral cavity. Evidence is emerging that these amino sugars provide ecological advantages to beneficial commensals over oral pathogens and pathobionts. Here, we performed transcriptome analysis on Streptococcus mutans and Streptococcus gordonii growing in single-species or dual-species cultures with glucose, GlcN or GlcNAc as the primary carbohydrate source. Compared to glucose, GlcN caused drastic transcriptomic shifts in each bacterium when they were cultured alone. Likewise, co-cultivation in the presence of GlcN yielded transcriptomic profiles that were dramatically different than the single-species results from GlcN-grown cells. In contrast, GlcNAc elicited only minor changes in the transcriptome of either organism in single- and dual-species cultures. Interestingly, genes involved in pyruvate metabolism were among the most significantly affected by GlcN in both species, and these changes were consistent with measurements of pyruvate in culture supernates. Differing from a previous report, growth of S. mutans alone with GlcN inhibited expression of multiple operons required for mutacin production. Co-cultivation with S. gordonii consistently increased the expression by S. mutans of two manganese transporter operons (slo and mntH) and decreased expression of mutacin genes. Conversely, S. gordonii appeared to be less affected by the presence of S. mutans, but did show increases in genes for biosynthetic processes in the co-cultures. In conclusion, amino sugars profoundly alter the interactions between a pathogenic and commensal streptococcus by reprogramming central metabolism.IMPORTANCECarbohydrate metabolism is central to the development of dental caries. A variety of sugars available to dental microorganisms influence the development of caries by affecting the physiology, ecology, and pathogenic potential of tooth biofilms. Using two well-characterized oral bacteria, one pathogen (Streptococcus mutans) and one commensal (Streptococcus gordonii) in a RNA deep-sequencing analysis, we studied the impact of two abundant amino sugars on bacterial gene expression and interspecies interactions. The results indicated large-scale remodeling of gene expression induced by GlcN in particular, affecting bacterial energy generation, acid production, protein synthesis, and release of antimicrobial molecules. Our study provides novel insights into how amino sugars modify bacterial behavior, information that will be valuable in the design of new technologies to detect and prevent oral infectious diseases.

scholarly journals Loss of NADH Oxidase Activity in Streptococcus mutans Leads to Rex-Mediated Overcompensation in NAD+Regeneration by Lactate Dehydrogenase

2015 ◽  
Vol 197 (23) ◽  
pp. 3645-3657 ◽  
Author(s):  
J. L. Baker ◽  
A. M. Derr ◽  
R. C. Faustoferri ◽  
R. G. Quivey
Keyword(s):  
Oxidative Stress ◽  
Lactate Dehydrogenase ◽  
Stress Response ◽  
Streptococcus Mutans ◽  
Parent Strain ◽  
Nadh Oxidase ◽  
Oral Streptococci ◽  
Pathogenic Potential ◽  
Oral Pathogen ◽  
Content Type

ABSTRACTPrevious studies of the oral pathogenStreptococcus mutanshave determined that this Gram-positive facultative anaerobe mounts robust responses to both acid and oxidative stresses. The water-forming NADH oxidase (Nox; encoded bynox) is thought to be critical for the regeneration of NAD+, for use in glycolysis, and for the reduction of oxygen, thereby preventing the formation of damaging reactive oxygen species. In this study, the free NAD+/NADH ratio in anoxdeletion strain (Δnox) was discovered to be remarkably higher than that in the parent strain, UA159, when the strains were grown in continuous culture. This unanticipated result was explained by significantly elevated lactate dehydrogenase (Ldh; encoded byldh) activity andldhtranscription in the Δnoxstrain, which was mediated in part by the redox-sensing regulator Rex. cDNA microarray analysis ofS. mutanscultures exposed to simultaneous acid stress (growth at a low pH) and oxidative stress (generated through the deletion ofnoxor the addition of exogenous oxygen) revealed a stress response synergistically heightened over that with either stress alone. In the Δnoxstrain, this elevated stress response included increased glucose phosphoenolpyruvate phosphotransferase system (PTS) activity, which appeared to be due to elevatedmanLtranscription, mediated in part, like elevatedldhtranscription, by Rex. While the Δnoxstrain does possess a membrane composition different from that of the parent strain, it did not appear to have defects in either membrane permeability or ATPase activity. However, the altered transcriptome and metabolome of the Δnoxstrain were sufficient to impair its ability to compete with commensal peroxigenic oral streptococci during growth under aerobic conditions.IMPORTANCEStreptococcus mutansis an oral pathogen whose ability to outcompete commensal oral streptococci is strongly linked to the formation of dental caries. Previous work has demonstrated that theS. mutanswater-forming NADH oxidase is critical for both carbon metabolism and the prevention of oxidative stress. The results of this study show that upregulation of lactate dehydrogenase, mediated through the redox sensor Rex, overcompensates for the loss ofnox. Additionally,noxdeletion led to the upregulation of mannose and glucose transport, also mediated through Rex. Importantly, the loss ofnoxrenderedS. mutansdefective in its ability to compete directly with two species of commensal streptococci, suggesting a role fornoxin the pathogenic potential of this organism.

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