scholarly journals Genome-wide identification of novel sRNAs in Streptococcus mutans

2021 ◽  
Author(s):  
Madeline Krieger ◽  
Justin Merritt ◽  
Rahul Raghavan
Keyword(s):  
Gene Regulation ◽  
Stress Response ◽  
Streptococcus Mutans ◽  
Oral Bacteria ◽  
Fine Tuning ◽  
Energetic Cost ◽  
Phosphotransferase System ◽  
Posttranscriptional Gene Regulation ◽  
Oral Biofilms

Streptococcus mutans is a major pathobiont involved in the development of dental caries. Its ability to utilize numerous sugars and to effectively respond to environmental stress promotes S. mutans proliferation in oral biofilms. Because of their quick action and low energetic cost, non-coding small RNAs (sRNAs) represent an ideal mode of gene regulation in stress response networks, yet their roles in oral pathogens have remained largely unexplored. We identified 15 novel sRNAs in S. mutans and show that they respond to four stress-inducing conditions commonly encountered by the pathogen in human mouth: sugar-phosphate stress, hydrogen peroxide exposure, high temperature, and low pH. To better understand the role of sRNAs in S. mutans, we further explored the function of the novel sRNA, SmsR4. Our data demonstrate that SmsR4 regulates the EIIA component of the sorbitol phosphotransferase system, which transports and phosphorylates the sugar alcohol sorbitol. The fine-tuning of EIIA availability by SmsR4 likely promotes S. mutans growth while using sorbitol as the main carbon source. Our work lays a foundation for understanding the role of sRNAs in regulating gene expression in stress response networks in S. mutans and highlights the importance of the underexplored phenomenon of posttranscriptional gene regulation in oral bacteria.

scholarly journals Genetic and Physiologic Analysis of thegroE Operon and Role of the HrcA Repressor in Stress Gene Regulation and Acid Tolerance in Streptococcus mutans

2001 ◽  
Vol 183 (20) ◽  
pp. 6074-6084 ◽  
Author(s):  
José A. C. Lemos ◽  
Yi-Ywan M. Chen ◽  
Robert A. Burne
Keyword(s):  
Streptococcus Mutans ◽  
Acid Tolerance ◽  
Oral Bacteria ◽  
Mrna Levels ◽  
Acid Shock ◽  
Oral Biofilms ◽  
In The Wild ◽  
Dnak Protein ◽  
Stress Gene

ABSTRACT Our working hypothesis is that the major molecular chaperones DnaK and GroE play central roles in the ability of oral bacteria to cope with the rapid and frequent stresses encountered in oral biofilms, such as acidification and nutrient limitation. Previously, our laboratory partially characterized the dnaK operon ofStreptococcus mutans(hrcA-grpE-dnaK) and demonstrated that dnaK is up-regulated in response to acid shock and sustained acidification (G. C. Jayaraman, J. E. Penders, and R. A. Burne, Mol. Microbiol. 25:329–341, 1997). Here, we show that thegroESL genes of S. mutans constitute an operon that is expressed from a stress-inducible ςA-type promoter located immediately upstream of a CIRCE element. GroEL protein and mRNA levels were elevated in cells exposed to a variety of stresses, including acid shock. A nonpolar insertion into hrcA was created and used to demonstrate that HrcA negatively regulates the expression of thegroEL and dnaK operons. The SM11 mutant, which had constitutively high levels of GroESL and roughly 50% of the DnaK protein found in the wild-type strain, was more sensitive to acid killing and could not lower the pH as effectively as the parent. The acid-sensitive phenotype of SM11 was, at least in part, attributable to lower F1F0-ATPase activity. A minimum of 10 proteins, in addition to GroES-EL, were found to be up-regulated in SM11. The data clearly indicate that HrcA plays a key role in the regulation of chaperone expression in S. mutans and that changes in the levels of the chaperones profoundly influence acid tolerance.

Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation

Science ◽  
2018 ◽  
Vol 361 (6403) ◽  
pp. 701-704 ◽  
Author(s):  
Jaechul Lim ◽  
Dongwan Kim ◽  
Young-suk Lee ◽  
Minju Ha ◽  
Mihye Lee ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Half Life ◽  
Messenger Rna ◽  
Mrna Translation ◽  
Posttranscriptional Gene Regulation ◽  
And Function ◽  
Mrna Half Life ◽  
In Cells

RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3′ end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.

scholarly journals Metabolic and Community Synergy of Oral Bacteria in Colorectal Cancer

mSphere ◽  
2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Kaitlin J. Flynn ◽  
Nielson T. Baxter ◽  
Patrick D. Schloss
Keyword(s):  
Colorectal Cancer ◽  
Fusobacterium Nucleatum ◽  
Oral Bacteria ◽  
Oral Microbiota ◽  
Community Members ◽  
Content Type ◽  
Bacterial Physiology ◽  
Oral Biofilms ◽  
Two Factors

ABSTRACT The oral periodontopathic bacterium Fusobacterium nucleatum has been repeatedly associated with colorectal tumors. Molecular analysis has identified specific virulence factors that promote tumorigenesis in the colon. However, other oral community members, such as members of the Porphyromonas spp., are also found with F. nucleatum on colonic tumors, and thus, narrow studies of individual pathogens do not take community-wide virulence properties into account. A broader view of oral bacterial physiology and pathogenesis identifies two factors that could promote colonization and persistence of oral bacterial communities in the colon. The polymicrobial nature of oral biofilms and the asaccharolytic metabolism of many of these species make them well suited to life in the microenvironment of colonic lesions. Consideration of these two factors offers a novel perspective on the role of oral microbiota in the initiation, development, and treatment of colorectal cancer.

scholarly journals MicroRNAs in skin and wound healing

2011 ◽  
Vol 43 (10) ◽  
pp. 543-556 ◽  
Author(s):  
Jaideep Banerjee ◽  
Yuk Cheung Chan ◽  
Chandan K. Sen
Keyword(s):  
Wound Healing ◽  
Gene Regulation ◽  
Skin Diseases ◽  
Mrna Degradation ◽  
Messenger Rnas ◽  
Skin Development ◽  
Rna Molecules ◽  
Posttranscriptional Gene Regulation

MicroRNAs (miRNAs) are small endogenous RNA molecules ∼22 nt in length. miRNAs are capable of posttranscriptional gene regulation by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of translation. miRNAs have recently been shown to play pivotal roles in skin development and are linked to various skin pathologies, cancer, and wound healing. This review focuses on the role of miRNAs in cutaneous biology, the various methods of miRNA modulation, and the therapeutic opportunities in treatment of skin diseases and wound healing.

scholarly journals Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR

2021 ◽  
Vol 7 (22) ◽  
pp. eabf0971
Author(s):  
Sophie Kaspar ◽  
Christian Oertlin ◽  
Karolina Szczepanowska ◽  
Alexandra Kukat ◽  
Katharina Senft ◽  
...  
Keyword(s):  
Stress Response ◽  
Mitochondrial Gene ◽  
Transcriptional Response ◽  
Premature Death ◽  
Fine Tuning ◽  
Mitochondrial Stress ◽  
Respiratory Chain Deficiency ◽  
Unfolded Protein ◽  
Protein Response

In response to disturbed mitochondrial gene expression and protein synthesis, an adaptive transcriptional response sharing a signature of the integrated stress response (ISR) is activated. We report an intricate interplay between three transcription factors regulating the mitochondrial stress response: CHOP, C/EBPβ, and ATF4. We show that CHOP acts as a rheostat that attenuates prolonged ISR, prevents unfavorable metabolic alterations, and postpones the onset of mitochondrial cardiomyopathy. Upon mitochondrial dysfunction, CHOP interaction with C/EBPβ is needed to adjust ATF4 levels, thus preventing overactivation of the ATF4-regulated transcriptional program. Failure of this interaction switches ISR from an acute to a chronic state, leading to early respiratory chain deficiency, energy crisis, and premature death. Therefore, contrary to its previously proposed role as a transcriptional activator of mitochondrial unfolded protein response, our results highlight a role of CHOP in the fine-tuning of mitochondrial ISR in mammals.

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 Dynamic mRNA modifications: An emerging layer of gene regulation

2015 ◽  
Vol 37 (2) ◽  
pp. 14-18 ◽  
Author(s):  
Adrian Whitehouse
Keyword(s):  
Gene Regulation ◽  
Messenger Rna ◽  
Fine Tuning ◽  
Minor Role ◽  
Small Nuclear Rna ◽  
Non Coding Rna ◽  
A Minor ◽  
And Function ◽  
Long Non Coding Rna

More than 100 different types of chemical modifications are found in cellular RNAs, including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA) and small nuclear RNA (snRNA). Internal modifications of mRNA were first observed in the 1970s, but, until recently, the role of these mRNA modifications has been a largely neglected field. A long-standing view was that mRNA modifications were static and unalterable, having a minor role in fine-tuning the structure and function of mRNAs. However, recent exciting discoveries now suggest that certain mRNA modifications are dynamic and, in some cases, reversible. Therefore they may have critical regulatory roles in gene expression, analogous to those which dynamically regulate DNA and protein modifications. As such, understanding the scope and mechanisms of these dynamic mRNA modifications represents an emerging layer of gene regulation at the RNA level, termed epitranscriptomics or RNA epigenetics.

scholarly journals Diversity in Antagonistic Interactions between Commensal Oral Streptococci and Streptococcus mutans

2017 ◽  
Vol 52 (1-2) ◽  
pp. 88-101 ◽  
Author(s):  
Xuelian Huang ◽  
Christopher M. Browngardt ◽  
Min Jiang ◽  
Sang-Joon Ahn ◽  
Robert A. Burne ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Oral Bacteria ◽  
Anaerobic Growth ◽  
Growth Media ◽  
H2o2 Production ◽  
Oral Streptococci ◽  
Carbohydrate Source ◽  
Antagonistic Effects ◽  
Oral Biofilms ◽  
Antagonistic Interactions

Arginine metabolism via the arginine deiminase system (ADS) of oral bacteria generates ammonia, which can increase the pH of oral biofilms and decrease the risk for dental caries. Antagonistic interactions between ADS-positive and cariogenic bacteria in oral biofilms may be an important ecological determinant of caries. This study investigated the antagonistic potential and mechanisms of clinical isolates of arginolytic streptococci on and by Streptococcus mutans UA159, a well-characterized cariogenic human isolate. Low-passage isolates of Streptococcus gordonii, Streptococcus sanguinis, Streptococcus parasanguinis, Streptococcus australis, and Streptococcus cristatus inhibited the growth of S. mutans to various degrees when they were inoculated on growth media first or simultaneously with S. mutans. The antagonistic effects of arginolytic strains against S. mutans and the production of H2O2 by these strains were enhanced during growth in a less-rich medium or when galactose was substituted for glucose as the primary carbohydrate source. Pyruvate oxidase was the dominant pathway for H2O2 production by arginolytic strains, but lactate oxidase activity was also detected in some strains of S. gordonii and S. cristatus. UA159 inhibited the growth of all tested arginolytic strains when inoculated first, especially in aerobic conditions. However, the antagonistic effects of S. mutans on certain strains of S. gordonii and S. australis were not observed during anaerobic growth in the presence of arginine. Thus, arginolytic commensal streptococci may have a synergistically positive impact on the ecology of oral biofilms by moderating biofilm pH while antagonizing the growth and virulence of caries pathogens.

scholarly journals Stress-Induced Membrane Association of the Streptococcus mutans GTP-Binding Protein, an Essential G Protein, and Investigation of Its Physiological Role by Utilizing an Antisense RNA Strategy

1999 ◽  
Vol 67 (9) ◽  
pp. 4510-4516 ◽  
Author(s):  
Didi Baev ◽  
Reg England ◽  
Howard K. Kuramitsu
Keyword(s):  
Elevated Temperature ◽  
Stress Response ◽  
Streptococcus Mutans ◽  
Antisense Rna ◽  
Binding Protein ◽  
Physiological Role ◽  
Acidic Ph ◽  
Gtp Binding Protein ◽  
Gtp Binding

ABSTRACT SGP (for Streptococcus GTP-binding protein) is aStreptococcus mutans essential GTPase which has significant sequence identity to the previously identified Escherichia coli Era protein and to numerous other prokaryotic GTPase proteins of unknown function. Recent studies in our laboratory have addressed the possible role of SGP in the stress response of the oral pathogen S. mutans. Here we report that during growth in the early stationary phase, and in response to elevated temperatures or acidic pH, the distribution of SGP between the cytoplasm and the membranes of S. mutans cells varies. Immunoblot analysis of soluble and membrane protein fractions collected from the mid-log and early stationary growth phases of bacterial populations grown at normal temperature (37°C) and at the elevated temperature of 43°C, or at acidic pH, demonstrated that the total amount of SGP increased with the age of the bacterial culture, elevated temperature, or acidic pH. Furthermore, it was established that a substantial amount of SGP is associated with the membrane fraction under stress conditions. In order to investigate the physiological role of SGP, we constructed anS. mutans strain capable of chromosomalsgp antisense RNA expression, which interferes with the normal information processing of the sgp gene. Utilizing this strain, we determined conditions whereby the streptococcal cells can be depleted of SGP, thus avoiding the problem of constructing a conditional lethal system. From the results of measurements of the nucleotide pools extracted from the antisense strain and its isogenic counterpart, we propose that one of the physiological roles of SGP is regulation and modulation of the GTP/GDP ratio under different growth conditions. Moreover, we observed that in SGP-depleted cells the levels of glucan-binding protein A (GbpA) substantially increased, suggesting that GbpA may have stress response-related physiological functions. Finally, the potential applications of the antisense RNA approach that we employed are discussed.

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