scholarly journals Effects of Oxygen on Virulence Traits of Streptococcus mutans

2007 ◽  
Vol 189 (23) ◽  
pp. 8519-8527 ◽  
Author(s):  
Sang-Joon Ahn ◽  
Zezhang T. Wen ◽  
Robert A. Burne
Keyword(s):  
Streptococcus Mutans ◽  
Regulatory Networks ◽  
Nadh Oxidase ◽  
Tricarboxylic Acid Cycle ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Virulence Traits ◽  
Oral Biofilms ◽  
Underlying Mechanisms ◽  
Upregulated Genes

ABSTRACT Oxygen profoundly affects the composition of oral biofilms. Recently, we showed that exposure of Streptococcus mutans to oxygen strongly inhibits biofilm formation and alters cell surface biogenesis. To begin to dissect the underlying mechanisms by which oxygen affects known virulence traits of S. mutans, transcription profiling was used to show that roughly 5% of the genes of this organism are differentially expressed in response to aeration. Among the most profoundly upregulated genes were autolysis-related genes and those that encode bacteriocins, the ClpB protease chaperone subunit, pyruvate dehydrogenase, the tricarboxylic acid cycle enzymes, NADH oxidase enzymes, and certain carbohydrate transporters and catabolic pathways. Consistent with our observation that the ability of S. mutans to form biofilms was severely impaired by oxygen exposure, transcription of the gtfB gene, which encodes one of the primary enzymes involved in the production of water-insoluble, adhesive glucan exopolysaccharides, was down-regulated in cells growing aerobically. Further investigation revealed that transcription of gtfB, but not gtfC, was responsive to oxygen and that aeration causes major changes in the amount and degree of cell association of the Gtf enzymes. Moreover, inactivation of the VicK sensor kinase affected the expression and localization the GtfB and GtfC enzymes. This study provides novel insights into the complex transcriptional and posttranscriptional regulatory networks used by S. mutans to modulate virulence gene expression and exopolysaccharide production in response to changes in oxygen availability.

scholarly journals The Streptococcus mutans Cid and Lrg systems modulate virulence traits in response to multiple environmental signals

Microbiology ◽  
2010 ◽  
Vol 156 (10) ◽  
pp. 3136-3147 ◽  
Author(s):  
Sang-Joon Ahn ◽  
Kelly C. Rice ◽  
Janneth Oleas ◽  
Kenneth W. Bayles ◽  
Robert A. Burne
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Protein A ◽  
Virulence Gene ◽  
Structural Features ◽  
Exponential Phase ◽  
Late Exponential Phase ◽  
Environmental Signals ◽  
Virulence Gene Expression ◽  
Virulence Traits

The tight control of autolysis by Streptococcus mutans is critical for proper virulence gene expression and biofilm formation. A pair of dicistronic operons, SMU.575/574 (lrgAB) and SMU.1701/1700 (designated cidAB), encode putative membrane proteins that share structural features with the bacteriophage-encoded holin family of proteins, which modulate host cell lysis during lytic infection. Analysis of S. mutans lrg and cid mutants revealed a role for these operons in autolysis, biofilm formation, glucosyltransferase expression and oxidative stress tolerance. Expression of lrgAB was repressed during early exponential phase and was induced over 1000-fold as cells entered late exponential phase, whereas cidAB expression declined from early to late exponential phase. A two-component system encoded immediately upstream of lrgAB (LytST) was required for activation of lrgAB expression, but not for cid expression. In addition to availability of oxygen, glucose levels were revealed to affect lrg and cid transcription differentially and significantly, probably through CcpA (carbon catabolite protein A). Collectively, these findings demonstrate that the Cid/Lrg system can affect several virulence traits of S. mutans, and its expression is controlled by two major environmental signals, oxygen and glucose. Moreover, cid/lrg expression is tightly regulated by LytST and CcpA.

scholarly journals Pathovar Transcriptomes

mSystems ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Amy Platenkamp ◽  
Jay L. Mellies
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Regulatory Networks ◽  
Virulence Gene ◽  
Model System ◽  
Genomic Sequences ◽  
Bacterial Strains ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Link Type

ABSTRACT Archetypal pathogenic bacterial strains are often used to elucidate regulatory networks of an entire pathovar, which encompasses multiple lineages and phylogroups. With enteropathogenic Escherichia coli (EPEC) as a model system, Hazen and colleagues (mSystems 6:e00024-17, 2017, https://doi.org/10.1128/mSystems.00024-17 ) used 9 isolates representing 8 lineages and 3 phylogroups to find that isolates with similar genomic sequences exhibit similarities in global transcriptomes under conditions of growth in medium that induces virulence gene expression, and they found variation among individual isolates. Archetypal pathogenic bacterial strains are often used to elucidate regulatory networks of an entire pathovar, which encompasses multiple lineages and phylogroups. With enteropathogenic Escherichia coli (EPEC) as a model system, Hazen and colleagues (mSystems 6:e00024-17, 2017, https://doi.org/10.1128/mSystems.00024-17 ) used 9 isolates representing 8 lineages and 3 phylogroups to find that isolates with similar genomic sequences exhibit similarities in global transcriptomes under conditions of growth in medium that induces virulence gene expression. They also found variation among individual isolates. Their work illustrates the importance of moving beyond observing regulatory phenomena of a limited number of regulons in a few archetypal strains, with the possibility of correlating clinical symptoms to key transcriptional pathways across lineages and phylogroups.

VicRK and CovR polymorphisms in Streptococcus mutans strains associated with cardiovascular infections

2021 ◽  
Vol 70 (12) ◽  
Author(s):  
Letícia T. Oliveira ◽  
Lívia A. Alves ◽  
Erika N. Harth-Chu ◽  
Ryota Nomura ◽  
Kazuhiko Nakano ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Type Species ◽  
Virulence Gene ◽  
Common Species ◽  
Oral Microbiome ◽  
Nucleotide Polymorphisms ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Coding Regions ◽  
Link Type

Introduction. Streptococcus mutans , a common species of the oral microbiome, expresses virulence genes promoting cariogenic dental biofilms, persistence in the bloodstream and cardiovascular infections. Gap statement. Virulence gene expression is variable among S. mutans strains and controlled by the transcription regulatory systems VicRK and CovR. Aim. This study investigates polymorphisms in the vicRK and covR loci in S. mutans strains isolated from the oral cavity or from the bloodstream, which were shown to differ in expression of covR, vicRK and downstream genes. Methodology. The transcriptional activities of covR, vicR and vicK were compared by RT-qPCR between blood and oral strains after exposure to human serum. PCR-amplified promoter and/or coding regions of covR and vicRK of 18 strains (11 oral and 7 blood) were sequenced and compared to the reference strain UA159. Results. Serum exposure significantly reduced covR and vicR/K transcript levels in most strains (P<0.05), but reductions were higher in oral than in blood strains. Single-nucleotide polymorphisms (SNPs) were detected in covR regulatory and coding regions, but SNPs affecting the CovR effector domain were only present in two blood strains. Although vicR was highly conserved, vicK showed several SNPs, and SNPs affecting VicK regions important for autokinase activity were found in three blood strains. Conclusions. This study reveals transcriptional and structural diversity in covR and vicR/K, and identifies polymorphisms of functional relevance in blood strains, indicating that covR and vicRK might be important loci for S. mutans adaptation to host selective pressures associated with virulence diversity.

scholarly journals The SloR/Dlg Metalloregulator Modulates Streptococcus mutans Virulence Gene Expression

2006 ◽  
Vol 188 (14) ◽  
pp. 5033-5044 ◽  
Author(s):  
Elizabeth Rolerson ◽  
Adam Swick ◽  
Lindsay Newlon ◽  
Cameron Palmer ◽  
Yong Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Streptococcus Mutans ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Virulence Gene ◽  
Wild Type ◽  
Genetic Competence ◽  
Virulence Gene Expression ◽  
Metal Ion Homeostasis

ABSTRACT Metal ion availability in the human oral cavity plays a putative role in Streptococcus mutans virulence gene expression and in appropriate formation of the plaque biofilm. In this report, we present evidence that supports such a role for the DtxR-like SloR metalloregulator (called Dlg in our previous publications) in this oral pathogen. Specifically, the results of gel mobility shift assays revealed the sloABC, sloR, comDE, ropA, sod, and spaP promoters as targets of SloR binding. We confirmed differential expression of these genes in a GMS584 SloR-deficient mutant versus the UA159 wild-type progenitor by real-time semiquantitative reverse transcriptase PCR experiments. The results of additional expression studies support a role for SloR in S. mutans control of glucosyltransferases, glucan binding proteins, and genes relevant to antibiotic resistance. Phenotypic analysis of GMS584 revealed that it forms aberrant biofilms on an abiotic surface, is compromised for genetic competence, and demonstrates heightened incorporation of iron and manganese as well as resistance to oxidative stress compared to the wild type. Taken together, these findings support a role for SloR in S. mutans adherence, biofilm formation, genetic competence, metal ion homeostasis, oxidative stress tolerance, and antibiotic gene regulation, all of which contribute to S. mutans-induced disease.

scholarly journals Regulatory Networks Controlling Vibrio cholerae Virulence Gene Expression

2007 ◽  
Vol 75 (12) ◽  
pp. 5542-5549 ◽  
Author(s):  
Jyl S. Matson ◽  
Jeffrey H. Withey ◽  
Victor J. DiRita
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Regulatory Networks ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals Elevated microglial oxidative phosphorylation and phagocytosis stimulate post-stroke brain remodeling and cognitive function recovery in mice

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Shanshan Song ◽  
Lauren Yu ◽  
Md Nabiul Hasan ◽  
Satya S. Paruchuri ◽  
Steven J. Mullett ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Oxidative Phosphorylation ◽  
Aerobic Glycolysis ◽  
Tricarboxylic Acid Cycle ◽  
Post Stroke ◽  
Pathway Activation ◽  
Function Recovery ◽  
Underlying Mechanisms ◽  
New Research ◽  
Upregulated Genes

AbstractNew research shows that disease-associated microglia in neurodegenerative brains present features of elevated phagocytosis, lysosomal functions, and lipid metabolism, which benefit brain repair. The underlying mechanisms remain poorly understood. Intracellular pH (pHi) is important for regulating aerobic glycolysis in microglia, where Na/H exchanger (NHE1) is a key pH regulator by extruding H+ in exchange of Na+ influx. We report here that post-stroke Cx3cr1-CreER+/−;Nhe1flox/flox (Nhe1 cKO) brains displayed stimulation of microglial transcriptomes of rate-limiting enzyme genes for glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. The other upregulated genes included genes for phagocytosis and LXR/RXR pathway activation as well as the disease-associated microglia hallmark genes (Apoe, Trem2, Spp1). The cKO microglia exhibited increased oxidative phosphorylation capacity, and higher phagocytic activity, which likely played a role in enhanced synaptic stripping and remodeling, oligodendrogenesis, and remyelination. This study reveals that genetic blockade of microglial NHE1 stimulated oxidative phosphorylation immunometabolism, and boosted phagocytosis function which is associated with tissue remodeling and post-stroke cognitive function recovery.

scholarly journals Effects of resveratrol on cariogenic virulence properties of Streptococcus mutans

2020 ◽  
Author(s):  
Jinheng Li ◽  
Tiantian Wu ◽  
Weiwei Peng ◽  
yaqin zhu
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Acid Production ◽  
Virulence Gene ◽  
Acid Tolerance ◽  
Extracellular Polysaccharide ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
Virulence Gene Expression ◽  
Virulence Properties

Abstract Background: Streptococcus mutans is the principal etiological agent of human dental caries. The major virulence factors of S. mutans are acid production, acid tolerance, extracellular polysaccharide (EPS) synthesis and biofilm formation. The aim of this study is to evaluate the effect of resveratrol, a natural compound, on virulence properties of S. mutans . Results: Resveratrol at sub-MIC levels significantly decreased acid production and acid tolerance, inhibited synthesis of water-soluble polysaccharide and water-insoluble polysaccharide, compromised biofilm formation. Related virulence gene expression ( ldh, relA, gtfC, comDE ) was down-regulated with increasing concentrations of resveratrol. Conclusions : Resveratrol has an inhibitory effect on S. mutans cariogenic virulence properties and it represents a promising anticariogenic agent. Keywords : resveratrol, Streptococcus mutans , acidogenicity, aciduricity, extracellular polysaccharide, biofilm

scholarly journals Interactions of the Metalloregulatory Protein SloR from Streptococcus mutans with Its Metal Ion Effectors and DNA Binding Site

2015 ◽  
Vol 197 (22) ◽  
pp. 3601-3615 ◽  
Author(s):  
Grace Spatafora ◽  
John Corbett ◽  
Louis Cornacchione ◽  
William Daly ◽  
Diego Galan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Real Time ◽  
Streptococcus Mutans ◽  
Metal Ion ◽  
Virulence Gene ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Metal Ion Homeostasis ◽  
Binding Interface

ABSTRACTStreptococcus mutansis the causative agent of dental caries, a significant concern for human health, and therefore an attractive target for therapeutics development. Previous work in our laboratory has identified a homodimeric, manganese-dependent repressor protein, SloR, as an important regulator of cariogenesis and has used site-directed mutagenesis to map functions to specific regions of the protein. Here we extend those studies to better understand the structural interaction between SloR and its operator and its effector metal ions. The results of DNase I assays indicate that SloR protects a 42-bp region of DNA that overlaps thesloABCpromoter on theS. mutansUA159 chromosome, while electrophoretic mobility shift and solution binding assays indicate that each of two SloR dimers binds to this region. Real-time semiquantitative reverse transcriptase PCR (real-time semi-qRT-PCR) experiments were used to determine the individual base pairs that contribute to SloR-DNA binding specificity. Solution studies indicate that Mn2+is better than Zn2+at specifically activating SloR to bind DNA, and yet the 2.8-Å resolved crystal structure of SloR bound to Zn2+provides insight into the means by which selective activation by Mn2+may be achieved and into how SloR may form specific interactions with its operator. Taken together, these experimental observations are significant because they can inform rational drug design aimed at alleviating and/or preventingS. mutans-induced caries formation.IMPORTANCEThis report focuses on investigating the SloR protein as a regulator of essential metal ion transport and virulence gene expression in the oral pathogenStreptococcus mutansand on revealing the details of SloR binding to its metal ion effectors and binding to DNA that together facilitate this expression. We used molecular and biochemical approaches to characterize the interaction of SloR with Mn2+and with its SloR recognition element to gain a clearer picture of the regulatory networks that optimize SloR-mediated metal ion homeostasis and virulence gene expression inS. mutans. These experiments can have a significant impact on caries treatment and/or prevention by revealing theS. mutansSloR-DNA binding interface as an appropriate target for the development of novel therapeutic interventions.

scholarly journals Manganese Affects Streptococcus mutans Virulence Gene Expression

2007 ◽  
Vol 41 (6) ◽  
pp. 503-511 ◽  
Author(s):  
P. Arirachakaran ◽  
E. Benjavongkulchai ◽  
S. Luengpailin ◽  
D. Ajdić ◽  
J.A. Banas
Keyword(s):  
Gene Expression ◽  
Streptococcus Mutans ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals The SloR/Dlg Metalloregulator Modulates Streptococcus mutans Virulence Gene Expression

2006 ◽  
Vol 188 (18) ◽  
pp. 6718-6718
Author(s):  
Elizabeth Rolerson ◽  
Adam Swick ◽  
Lindsay Newlon ◽  
Cameron Palmer ◽  
Yong Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Streptococcus Mutans ◽  
Virulence Gene ◽  
Virulence Gene Expression
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