Multiple factors regulate the expression of in .

Introduction: The gene cluster, encoding the sole iron-sulfur (Fe-S) cluster assembly system in , was recently shown to be up-regulated in response to oxidative stressors and Fe limitation.

Methods: In this study, luciferase reporter fusion assays, electrophoretic gel mobility shift assays (EMSA) and transcription assays (IVT) were used to dissect the and acting factors that regulate the expression of .

Results And Discussion: Results showed deletion of , for the only Fur-family transcriptional regulator in , resulted in >5-fold increases in luciferase activity under the control of the promoter (P<0.

SloR-SRE binding to the promoter is cooperative.

is a commensal member of the plaque microbiome. It is especially prevalent when dietary sugars are available for fermentation, generating acid byproducts that lower plaque pH and foster tooth decay. can survive in the transient conditions of the mouth, in part because it can regulate the uptake of manganese and iron during periods of feast when metal ions are available, and famine when they are limiting.

The Evolving Microbiome of Dental Caries.

Dental caries is a significant oral and public health problem worldwide, especially in low-income populations. The risk of dental caries increases with frequent intake of dietary carbohydrates, including sugars, leading to increased acidity and disruption of the symbiotic diverse and complex microbial community of health. Excess acid production leads to a dysbiotic shift in the bacterial biofilm composition, demineralization of tooth structure, and cavities.

Small regulatory RNAs are mediators of the SloR regulon.

Dental caries is among the most prevalent chronic diseases worldwide. , the chief causative agent of caries, uses a 25-kDa manganese-dependent SloR protein to coordinate the uptake of essential manganese with the transcription of its virulence attributes. Small non-coding RNAs (sRNAs) can either enhance or repress gene expression, and reports in the literature ascribe an emerging role for sRNAs in the environmental stress response.

Small regulatory RNAs are mediators of the SloR regulon.

Unlabelled: Dental caries is among the most prevalent chronic infectious diseases worldwide. , the chief causative agent of caries, uses a 25 kDa manganese dependent SloR protein to coordinate the uptake of essential manganese with the transcription of its virulence attributes. Small non-coding RNAs (sRNAs) can either enhance or repress gene expression and reports in the literature ascribe an emerging role for sRNAs in the environmental stress response.

Regulatory involvement of the PerR and SloR metalloregulators in the oxidative stress response.

is a commensal of the human oral microbiome that can promote dental caries under conditions of dysbiosis. This study investigates metalloregulators and their involvement in the oxidative stress response. Oxidative stress in the human mouth can derive from temporal increases in reactive oxygen species (ROS) after meal consumption and from endogenous bacterial ROS-producers that colonize the dentition.

The S. mutans mntE gene encodes a manganese efflux transporter.

Streptococcus mutans is a colonizer of the human dentition, and under conditions of dysbiosis is the primary causative agent of dental caries. The pathogenic potential of S. mutans depends, in part, on its ability to regulate the transport of metal ions across the plasma membrane to maintain intracellular metal ion homeostasis.

Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of Streptococcus mutans.

Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen To better understand the importance of manganese homeostasis to pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were those of the entire operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, here , that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of , which encodes the lipoprotein receptor of the SloABC system, or of alone had no major consequence for the overall fitness of , simultaneous inactivation of and (Δ Δ) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin.

Autoregulation of the Streptococcus mutans SloR Metalloregulator Is Constitutive and Driven by an Independent Promoter.

, one of ∼600 bacterial species in the human oral cavity, is among the most acidogenic constituents of the plaque biofilm. Considered to be the primary causative agent of dental caries, harbors a 25-kDa SloR metalloregulatory protein which controls metal ion transport across the bacterial cell membrane to maintain essential metal ion homeostasis. The expression of SloR derives in part from transcriptional readthrough of the operon, which encodes a Mn/Fe ABC transport system.

Transcriptional Profiling of the Oral Pathogen in Response to Competence Signaling Peptide XIP.

In the cariogenic , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the transcriptome.

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

Unlabelled: Streptococcus mutans is 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.

In vitro manganese-dependent cross-talk between Streptococcus mutans VicK and GcrR: implications for overlapping stress response pathways.

Streptococcus mutans, a major acidogenic component of the dental plaque biofilm, has a key role in caries etiology. Previously, we demonstrated that the VicRK two-component signal transduction system modulates biofilm formation, oxidative stress and acid tolerance responses in S. mutans.

Characterization of the functional domains of the SloR metalloregulatory protein in Streptococcus mutans.

Streptococcus mutans is a commensal member of the healthy plaque biofilm and the primary causative agent of dental caries. The present study is an investigation of SloR, a 25-kDa metalloregulatory protein that modulates genes responsible for S. mutans-induced cariogenesis.

Genome-wide characterization of the SloR metalloregulome in Streptococcus mutans.

Streptococcus mutans is the primary causative agent of human dental caries, a ubiquitous infectious disease for which effective treatment strategies remain elusive. We investigated a 25-kDa SloR metalloregulatory protein in this oral pathogen, along with its target genes that contribute to cariogenesis. Previous studies have demonstrated manganese- and SloR-dependent repression of the sloABCR metal ion transport operon in S.

SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary.

Streptococcus mutans, the primary causative agent of human dental caries, grows as a biofilm on the tooth surface, where it metabolizes dietary carbohydrates and generates acid byproducts that demineralize tooth enamel. A drop in plaque pH stimulates an adaptive acid-tolerance response (ATR) in this oral pathogen that allows it to survive acid challenge at pHs as low as 3.0.

The Streptococcus mutans vicX gene product modulates gtfB/C expression, biofilm formation, genetic competence, and oxidative stress tolerance.

Streptococcus mutans is considered one of the primary etiologic agents of dental caries. Previously, we characterized the VicRK two-component signal transduction system, which regulates multiple virulence factors of S. mutans.

The SloR/Dlg metalloregulator modulates Streptococcus mutans virulence gene expression.

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.

A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development.

Bacteria exposed to transient host environments can elicit adaptive responses by triggering the differential expression of genes via two-component signal transduction systems. This study describes the vicRK signal transduction system in Streptococcus mutans. A vicK (putative histidine kinase) deletion mutant (SmuvicK) was isolated.

Effect of an orphan response regulator on Streptococcus mutans sucrose-dependent adherence and cariogenesis.

Streptococcus mutans is the principal acidogenic component of dental plaque that demineralizes tooth enamel, leading to dental decay. Cell-associated glucosyltransferases catalyze the sucrose-dependent synthesis of sticky glucan polymers that, together with glucan binding proteins, promote S. mutans adherence to teeth and cell aggregation.

Evidence that ORF3 at the Streptococcus parasanguis fimA locus encodes a thiol-specific antioxidant.

Streptococcus parasanguis is a primary colonizer of dental plaque and a major player in subacute bacterial endocarditis. In the present study, the authors report that an ORF (ORF3) located 77 bp downstream of the fimA operon on the S. parasanguis FW213 chromosome complements an Escherichia coli thiol peroxidase (tpx) mutation in glutamine synthetase (GS) protection assays and that GS is protected by the ORF3 gene product in S.

Expression of Streptococcus mutans fimA is iron-responsive and regulated by a DtxR homologue.

Iron uptake, transport and storage in Streptococcus mutans, the principal causative agent of human dental cavities, is unexplored despite early reports in the literature which predict a role for this trace metal in cariogenesis. Experiments in the authors' laboratory revealed several iron-responsive proteins in S. mutans, one of which reacted with a polyclonal antiserum directed against the FimA fimbrial adhesin from Streptococcus parasanguis on Western blots.