scholarly journals Emergent Properties in Streptococcus mutans Biofilms Are Controlled through Adhesion Force Sensing by Initial Colonizers

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Can Wang ◽  
Jiapeng Hou ◽  
Henny C. van der Mei ◽  
Henk J. Busscher ◽  
Yijin Ren
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Streptococcus Mutans ◽  
Adhesion Force ◽  
Emergent Properties ◽  
Initial Contact ◽  
Adhesion Forces ◽  
Content Type ◽  
Force Sensitivity ◽  
Biofilm Bacteria

ABSTRACT Bacterial adhesion is accompanied by altered gene expression, leading to “emergent” properties of biofilm bacteria that are alien to planktonic ones. With the aim of revealing the role of environmental adhesion forces in emergent biofilm properties, genes in Streptococcus mutans UA159 and a quorum-sensing-deficient mutant were identified that become expressed after adhesion to substratum surfaces. Using atomic force microscopy, adhesion forces of initial S. mutans colonizers on four different substrata were determined and related to gene expression. Adhesion forces upon initial contact were similarly low across different substrata, ranging between 0.2 and 1.2 nN regardless of the strain considered. Bond maturation required up to 21 s, depending on the strain and substratum surface involved, but stationary adhesion forces also were similar in the parent and in the mutant strain. However, stationary adhesion forces were largest on hydrophobic silicone rubber (19 to 20 nN), while being smallest on hydrophilic glass (3 to 4 nN). brpA gene expression in thin (34 to 48 μm) 5-h S. mutans UA159 biofilms was most sensitive to adhesion forces, while expression of gbpB and comDE expressions was weakly sensitive. ftf, gtfB, vicR, and relA expression was insensitive to adhesion forces. In thicker (98 to 151 μm) 24-h biofilms, adhesion-force-induced gene expression and emergent extracellular polymeric substance (EPS) production were limited to the first 20 to 30 μm above a substratum surface. In the quorum-sensing-deficient S. mutans, adhesion-force-controlled gene expression was absent in both 5- and 24-h biofilms. Thus, initial colonizers of substratum surfaces sense adhesion forces that externally trigger emergent biofilm properties over a limited distance above a substratum surface through quorum sensing. IMPORTANCE A new concept in biofilm science is introduced: “adhesion force sensitivity of genes,” defining the degree up to which expression of different genes in adhering bacteria is controlled by the environmental adhesion forces they experience. Analysis of gene expression as a function of height in a biofilm showed that the information about the substratum surface to which initially adhering bacteria adhere is passed up to a biofilm height of 20 to 30 μm above a substratum surface, highlighting the importance and limitations of cell-to-cell communication in a biofilm. Bacteria in a biofilm mode of growth, as opposed to planktonic growth, are responsible for the great majority of human infections, predicted to become the number one cause of death in 2050. The concept of adhesion force sensitivity of genes provides better understanding of bacterial adaptation in biofilms, direly needed for the design of improved therapeutic measures that evade the recalcitrance of biofilm bacteria to antimicrobials.

scholarly journals Influence of Adhesion Force onicaAandcidAGene Expression and Production of Matrix Components in Staphylococcus aureus Biofilms

2015 ◽  
Vol 81 (10) ◽  
pp. 3369-3378 ◽  
Author(s):  
Akshay K. Harapanahalli ◽  
Yun Chen ◽  
Jiuyi Li ◽  
Henk J. Busscher ◽  
Henny C. van der Mei
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Adhesion Force ◽  
Extracellular Dna ◽  
Cross Linking ◽  
Adhesion Forces ◽  
Content Type ◽  
Isogenic Mutant ◽  
Matrix Components

ABSTRACTThe majority of human infections are caused by biofilms. The biofilm mode of growth enhances the pathogenicity ofStaphylococcusspp. considerably, because once they adhere, staphylococci embed themselves in a protective, self-produced matrix of extracellular polymeric substances (EPSs). The aim of this study was to investigate the influence of forces of staphylococcal adhesion to different biomaterials onicaA(which regulates the production of EPS matrix components) andcidA(which is associated with cell lysis and extracellular DNA [eDNA] release) gene expression inStaphylococcus aureusbiofilms. Experiments were performed withS. aureusATCC 12600 and its isogenic mutant,S. aureusATCC 12600 Δpbp4, deficient in peptidoglycan cross-linking. Deletion ofpbp4was associated with greater cell wall deformability, while it did not affect the planktonic growth rate, biofilm formation, cell surface hydrophobicity, or zeta potential of the strains. The adhesion forces ofS. aureusATCC 12600 were the strongest on polyethylene (4.9 ± 0.5 nN), intermediate on polymethylmethacrylate (3.1 ± 0.7 nN), and the weakest on stainless steel (1.3 ± 0.2 nN). The production of poly-N-acetylglucosamine, eDNA presence, and expression oficaAgenes decreased with increasing adhesion forces. However, no relation between adhesion forces andcidAexpression was observed. The adhesion forces of the isogenic mutantS. aureusATCC 12600 Δpbp4(deficient in peptidoglycan cross-linking) were much weaker than those of the parent strain and did not show any correlation with the production of poly-N-acetylglucosamine, eDNA presence, or expression of theicaAandcidAgenes. This suggests that adhesion forces modulate the production of the matrix molecule poly-N-acetylglucosamine, eDNA presence, andicaAgene expression by inducing nanoscale cell wall deformation, with cross-linked peptidoglycan layers playing a pivotal role in this adhesion force sensing.

scholarly journals The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in Yersinia pestis during Planktonic Growth and Growth in Biofilms

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Jeremy T. Ritzert ◽  
George Minasov ◽  
Ryan Embry ◽  
Matthew J. Schipma ◽  
Karla J. F. Satchell
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Carbon Source ◽  
Cyclic Amp ◽  
Yersinia Pestis ◽  
Carbon Sources ◽  
Transcriptional Regulator ◽  
Receptor Protein ◽  
Content Type ◽  
Bacterial Physiology

ABSTRACT Cyclic AMP (cAMP) receptor protein (Crp) is an important transcriptional regulator of Yersinia pestis. Expression of crp increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Y. pestis Crp, we determined a 1.8-Å crystal structure of the protein-cAMP complex. We found that compared to Escherichia coli Crp, C helix amino acid substitutions in Y. pestis Crp did not impact the cAMP dependency of Crp to bind DNA promoters. To investigate Y. pestis Crp-regulated genes during plague pneumonia, we performed RNA sequencing on both wild-type and Δcrp mutant bacteria growing in planktonic and biofilm states in minimal media with glucose or glycerol. Y. pestis Crp was found to dramatically alter expression of hundreds of genes in a manner dependent upon carbon source and growth state. Gel shift assays confirmed direct regulation of the malT and ptsG promoters, and Crp was then linked to Y. pestis growth on maltose as a sole carbon source. Iron regulation genes ybtA and fyuA were found to be indirectly regulated by Crp. A new connection between carbon source and quorum sensing was revealed as Crp was found to regulate production of acyl-homoserine lactones (AHLs) through direct and indirect regulation of genes for AHL synthetases and receptors. AHLs were subsequently identified in the lungs of Y. pestis-infected mice when crp expression was highest in Y. pestis biofilms. Thus, in addition to the well-studied pla gene, other Crp-regulated genes likely have important functions during plague infection. IMPORTANCE Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen Y. pestis requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of nonglucose sugars, we found that Crp regulates genes for virulence, metal acquisition, and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, which responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.

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 The Formation of Streptococcus mutans Persisters Induced by the Quorum-Sensing Peptide Pheromone Is Affected by the LexA Regulator

2015 ◽  
Vol 197 (6) ◽  
pp. 1083-1094 ◽  
Author(s):  
Vincent Leung ◽  
Dragana Ajdic ◽  
Stephanie Koyanagi ◽  
Céline M. Lévesque
Keyword(s):  
Quorum Sensing ◽  
Streptococcus Mutans ◽  
Bacterial Species ◽  
Regulatory System ◽  
Bacterial Survival ◽  
Chronic Infections ◽  
Persister Cells ◽  
Gene Encoding ◽  
Content Type ◽  
Peptide Pheromone

The presence of multidrug-tolerant persister cells within microbial populations has been implicated in the resiliency of bacterial survival against antibiotic treatments and is a major contributing factor in chronic infections. The mechanisms by which these phenotypic variants are formed have been linked to stress response pathways in various bacterial species, but many of these mechanisms remain unclear. We have previously shown that in the cariogenic organismStreptococcus mutans, the quorum-sensing peptide CSP (competence-stimulating peptide) pheromone was a stress-inducible alarmone that triggered an increased formation of multidrug-tolerant persisters. In this study, we characterized SMU.2027, a CSP-inducible gene encoding a LexA ortholog. We showed that in addition to exogenous CSP exposure, stressors, including heat shock, oxidative stress, and ofloxacin antibiotic, were capable of triggering expression oflexAin an autoregulatory manner akin to that of LexA-like transcriptional regulators. We demonstrated the role of LexA and its importance in regulating tolerance toward DNA damage in a noncanonical SOS mechanism. We showed its involvement and regulatory role in the formation of persisters induced by the CSP-ComDE quorum-sensing regulatory system. We further identified key genes involved in sugar and amino acid metabolism, the clustered regularly interspaced short palindromic repeat (CRISPR) system, and autolysin from transcriptomic analyses that contribute to the formation of quorum-sensing-induced persister cells.

scholarly journals Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP

mSystems ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Iwona B. Wenderska ◽  
Andrew Latos ◽  
Benjamin Pruitt ◽  
Sara Palmer ◽  
Grace Spatafora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Stress Response ◽  
Heat Shock ◽  
Streptococcus Mutans ◽  
Potential Role ◽  
Stringent Response ◽  
Amino Acid Starvation ◽  
Genetic Competence ◽  
Content Type

ABSTRACT Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans, DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans, XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a potential role in competence shutoff. Together, our results provide further evidence that multiple stress response mechanisms are linked through the genetic competence signaling pathway in S. mutans. In the cariogenic Streptococcus mutans, 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 S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans, DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans, XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a potential role in competence shutoff. Together, our results provide further evidence that multiple stress response mechanisms are linked through the genetic competence signaling pathway in S. mutans.

scholarly journals Hierarchical Transcriptional Control of the LuxR Quorum-Sensing Regulon of Vibrio harveyi

2020 ◽  
Vol 202 (14) ◽  
Author(s):  
Ryan R. Chaparian ◽  
Alyssa S. Ball ◽  
Julia C. van Kessel
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Quorum Sensing ◽  
Cell Density ◽  
Regulatory Networks ◽  
Vibrio Harveyi ◽  
Sugar Transport ◽  
Content Type ◽  
Second Tier

ABSTRACT In vibrios, quorum sensing controls hundreds of genes that are required for cell density-specific behaviors including bioluminescence, biofilm formation, competence, secretion, and swarming motility. The central transcription factor in the quorum-sensing pathway is LuxR/HapR, which directly regulates ∼100 genes in the >400-gene regulon of Vibrio harveyi. Among these directly controlled genes are 15 transcription factors, which we predicted would comprise the second tier in the hierarchy of the LuxR regulon. We confirmed that LuxR binds to the promoters of these genes in vitro and quantified the extent of LuxR activation or repression of transcript levels. Transcriptome sequencing (RNA-seq) indicates that most of these transcriptional regulators control only a few genes, with the exception of MetJ, which is a global regulator. The genes regulated by these transcription factors are predicted to be involved in methionine and thiamine biosynthesis, membrane stability, RNA processing, c-di-GMP degradation, sugar transport, and other cellular processes. These data support a hierarchical model in which LuxR directly regulates 15 transcription factors that drive the second level of the gene expression cascade to influence cell density-dependent metabolic states and behaviors in V. harveyi. IMPORTANCE Quorum sensing is important for survival of bacteria in nature and influences the actions of bacterial groups. In the relatively few studied examples of quorum-sensing-controlled genes, these genes are associated with competition or cooperation in complex microbial communities and/or virulence in a host. However, quorum sensing in vibrios controls the expression of hundreds of genes, and their functions are mostly unknown or uncharacterized. In this study, we identify the regulators of the second tier of gene expression in the quorum-sensing system of the aquaculture pathogen Vibrio harveyi. Our identification of regulatory networks and metabolic pathways controlled by quorum sensing can be extended and compared to other Vibrio species to understand the physiology, ecology, and pathogenesis of these organisms.

scholarly journals In VivoProgrammed Gene Expression Based on Artificial Quorum Networks

2015 ◽  
Vol 81 (15) ◽  
pp. 4984-4992 ◽  
Author(s):  
Teng Chu ◽  
Yajun Huang ◽  
Mingyu Hou ◽  
Qiyao Wang ◽  
Jingfan Xiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Cell Density ◽  
Protective Antigen ◽  
Expression System ◽  
Edwardsiella Tarda ◽  
Content Type ◽  
Genetic Components ◽  
Wide Range

ABSTRACTThe quorum sensing (QS) system, as a well-functioning population-dependent gene switch, has been widely applied in many gene circuits in synthetic biology. In our work, an efficient cell density-controlled expression system (QS) was established via engineering of theVibrio fischeri luxI-luxRquorum sensing system. In order to achievein vivoprogrammed gene expression, a synthetic binary regulation circuit (araQS) was constructed by assembling multiple genetic components, including the quorum quenching protein AiiA and the arabinose promoter ParaBAD, into the QS system.In vitroexpression assays verified that the araQS system was initiated only in the absence of arabinose in the medium at a high cell density.In vivoexpression assays confirmed that the araQS system presented anin vivo-triggered and cell density-dependent expression pattern. Furthermore, the araQS system was demonstrated to function well in different bacteria, indicating a wide range of bacterial hosts for use. To explore its potential applicationsin vivo, the araQS system was used to control the production of a heterologous protective antigen in an attenuatedEdwardsiella tardastrain, which successfully evoked efficient immune protection in a fish model. This work suggested that the araQS system could program bacterial expressionin vivoand might have potential uses, including, but not limited to, bacterial vector vaccines.

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 Autoinducer-2-Regulated Genes in Streptococcus mutans UA159 and Global Metabolic Effect of the luxS Mutation

2007 ◽  
Vol 190 (1) ◽  
pp. 401-415 ◽  
Author(s):  
Helena Sztajer ◽  
André Lemme ◽  
Ramiro Vilchez ◽  
Stefan Schulz ◽  
Robert Geffers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Streptococcus Mutans ◽  
Bacterial Species ◽  
Regulatory Protein ◽  
Acid Tolerance ◽  
Null Mutant ◽  
Gram Positive ◽  
Signal Molecule ◽  
Autoinducer 2

ABSTRACT Autoinducer 2 (AI-2) is the only species-nonspecific autoinducer known in bacteria and is produced by both gram-negative and gram-positive organisms. Consequently, it is proposed to function as a universal quorum-sensing signal for interaction between bacterial species. AI-2 is produced as the by-product of a metabolic transformation carried out by the LuxS enzyme. To separate the metabolic function of the LuxS enzyme from the signaling role of AI-2, we carried out a global transcriptome analysis of a luxS null mutant culture of Streptococcus mutans UA159, an important cariogenic bacterium and a crucial component of the dental plaque biofilm community, in comparison to a luxS null mutant culture supplemented with chemically pure 4,5-dihydroxy-2,3-pentanedione, the precursor of AI-2. The data revealed fundamental changes in gene expression affecting 585 genes (30% of the genome) which could not be restored by the signal molecule AI-2 and are therefore not caused by quorum sensing but by lack of the transformation carried out by the LuxS enzyme in the activated methyl cycle. All functional classes of enzymes were affected, including genes known to be important for biofilm formation, bacteriocin synthesis, competence, and acid tolerance. At the same time, 59 genes were identified whose transcription clearly responded to the addition of AI-2. Some of them were related to protein synthesis, stress, and cell division. Three membrane transport proteins were upregulated which are not related to any of the known AI-2 transporters. Three transcription factors were identified whose transcription was stimulated repeatedly by AI-2 addition during growth. Finally, a global regulatory protein, the δ subunit of the RNA polymerase (rpoE), was induced 147-fold by AI-2, representing the largest differential gene expression observed. The data show that many phenotypes related to the luxS mutation cannot be ascribed to quorum sensing and have identified for the first time regulatory proteins potentially mediating AI-2-based signaling in gram-positive bacteria.

scholarly journals ThePseudomonas aeruginosaOrphan Quorum Sensing Signal Receptor QscR Regulates Global Quorum Sensing Gene Expression by Activating a Single Linked Operon

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Fengming Ding ◽  
Ken-Ichi Oinuma ◽  
Nicole E. Smalley ◽  
Amy L. Schaefer ◽  
Omar Hamwy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Quorum Sensing ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Null Mutant ◽  
Content Type ◽  
Single Operon

ABSTRACTPseudomonas aeruginosauses two acyl-homoserine lactone signals and two quorum sensing (QS) transcription factors, LasR and RhlR, to activate dozens of genes. LasR responds toN-3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and RhlR toN-butanoyl-homoserine lactone (C4-HSL). There is a thirdP. aeruginosaacyl-homoserine-lactone-responsive transcription factor, QscR, which acts to dampen or delay activation of genes by LasR and RhlR by an unknown mechanism. To better understand the role of QscR inP. aeruginosaQS, we performed a chromatin immunoprecipitation analysis, which showed this transcription factor bound the promoter of only a single operon of three genes linked toqscR, PA1895 to PA1897. Other genes that appear to be regulated by QscR in transcriptome studies were not direct targets of QscR. Deletion of PA1897 recapitulates the early QS activation phenotype of a QscR-null mutant, and the phenotype of a QscR-null mutant was complemented by PA1895-1897 but not by PA1897 alone. We conclude that QscR acts to modulate quorum sensing through regulation of a single operon, apparently raising the QS threshold of the population and providing a “brake” on QS autoinduction.IMPORTANCEQuorum sensing, a cell-cell communication system, is broadly distributed among bacteria and is commonly used to regulate the production of shared products. An important consequence of quorum sensing is a delay in production of certain products until the population density is high. The bacteriumPseudomonas aeruginosahas a particularly complicated quorum sensing system involving multiple signals and receptors. One of these receptors, QscR, downregulates gene expression, unlike the other receptors inP. aeruginosa. QscR does so by inducing the expression of a single operon whose function provides an element of resistance to a population reaching a quorum. This finding has importance for design of quorum sensing inhibitory strategies and can also inform design of synthetic biological circuits that use quorum sensing receptors to regulate gene expression.

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