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 Environmental modification via a quorum sensing molecule influences the social landscape of siderophore production

2017 ◽  
Vol 284 (1852) ◽  
pp. 20170200 ◽  
Author(s):  
Roman Popat ◽  
Freya Harrison ◽  
Ana C. da Silva ◽  
Scott A. S. Easton ◽  
Luke McNally ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Public Goods ◽  
Bacterial Species ◽  
Relative Fitness ◽  
Iron Starvation ◽  
Signal Molecule ◽  
Signalling Molecules ◽  
Signalling Molecule ◽  
The Impact ◽  
Social Trait

Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed ‘public goods’ because they are costly for individuals to produce and can be exploited by non-producers (cheats). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS, therefore, determines the cooperative phenotype of individuals, and influences conflict over public goods. In addition to their regulatory functions, many QS molecules have additional properties that directly modify the prevailing environment. This leads to the possibility that QS molecules could influence conflict over public goods indirectly through non-signalling effects, and the impact of this on social competition has not previously been explored. The Pseudomonas aeruginosa QS signal molecule PQS is a powerful chelator of iron which can cause an iron starvation response. Here, we show that PQS stimulates a concentration-dependent increase in the cooperative production of iron scavenging siderophores, resulting in an increase in the relative fitness of non-producing siderophore cheats. This is likely due to an increased cost of siderophore output by producing cells and a concurrent increase in the shared benefits, which accrue to both producers and cheats. Although PQS can be a beneficial signalling molecule for P. aeruginosa , our data suggest that it can also render a siderophore-producing population vulnerable to competition from cheating strains. More generally, our results indicate that the production of one social trait can indirectly affect the costs and benefits of another social trait.

scholarly journals Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by Streptococcus pneumoniae , Resulting in Hypervirulence

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Claudia Trappetti ◽  
Lauren J. McAllister ◽  
Austen Chen ◽  
Hui Wang ◽  
Adrienne W. Paton ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Quorum Sensing ◽  
Capsular Polysaccharide ◽  
The Body ◽  
Gram Negative Bacteria ◽  
Phosphotransferase System ◽  
Gram Positive ◽  
Gram Negative ◽  
Autoinducer 2 ◽  
Leloir Pathway

ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gram-negative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS ( S -ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae , sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype. IMPORTANCE S. pneumoniae is a Gram-positive bacterium frequently carried asymptomatically in the human nasopharynx. However, in a proportion of cases, it can spread to other sites of the body, causing life-threatening diseases that translate into massive global morbidity and mortality. Our data show that AI-2 signaling via FruA promotes the transition of the pneumococcus from colonization to invasion by facilitating the utilization of galactose, the principal sugar available in the upper respiratory tract. AI-2-mediated upregulation of Leloir pathway enzymes results in increased production of capsular polysaccharide and hypervirulence in a murine intranasal challenge model. This identifies the highly conserved FruA phosphotransferase system as a target for new antimicrobials based on the disruption of this generic quorum-sensing system.

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 Regulation of Quorum Sensing by RpoS inPseudomonas aeruginosa

2000 ◽  
Vol 182 (15) ◽  
pp. 4356-4360 ◽  
Author(s):  
Marvin Whiteley ◽  
Matthew R. Parsek ◽  
E. P. Greenberg
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Gene Transcription ◽  
Opportunistic Pathogen ◽  
Null Mutant ◽  
Global Regulators ◽  
Acylhomoserine Lactone ◽  
Sensing Systems

ABSTRACT The LasR-LasI and RhlR-RhlI quorum-sensing systems are global regulators of gene expression in the opportunistic pathogenPseudomonas aeruginosa. Previous studies suggest that the RhlR-RhlI system activates expression of rpoS. We constructed merodiploid strains of P. aeruginosa containing the native rpoS gene and an rpoS-lacZ fusion. Studies of lacZ transcription in these strains indicated that rpoS was not regulated by RhlR-RhlI. We also generated an rpoS null mutant. This rpoS mutant showed elevated levels of rhlI (but not rhlR) transcription, elevated levels of the RhlI-generated acylhomoserine lactone quorum-sensing signal, and elevated levels of RhlR-RhlI-regulated gene transcription. These findings indicate that there is a relationship between RpoS and quorum sensing, but rather than the RhlR-RhlI system influencing the expression ofrpoS, it appears that RpoS regulates rhlI.

scholarly journals Environmental modification via a quorum sensing molecule influences the social landscape of siderophore production

2016 ◽  
Author(s):  
Roman Popat ◽  
Freya Harrison ◽  
Ana C. da Silva ◽  
Scott A. S. Easton ◽  
Luke McNally ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Public Goods ◽  
Bacterial Species ◽  
Relative Fitness ◽  
Iron Starvation ◽  
Signal Molecule ◽  
Signalling Molecules ◽  
Signalling Molecule ◽  
The Impact ◽  
Social Trait

Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed ‘public goods’ because they are costly for individuals to produce and can be exploited by non-producers (‘cheats’). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS therefore determines the cooperative phenotype of individuals, and influences conflict over public goods. In addition to their regulatory functions, many QS molecules have additional properties that directly modify the prevailing environment. This leads to the possibility that QS molecules could influence conflict over public goods indirectly through nonsignalling effects, and the impact of this on social competition has not previously been explored. ThePseudomonas aeruginosaQS signal molecule PQS is a powerful chelator of iron which can cause an iron starvation response. Here we show that PQS stimulates a concentration-dependent increase in the cooperative production of iron scavenging siderophores, resulting in an increase in the relative fitness of non-producing siderophore cheats. This is likely due to an increased cost of siderophore output by producing cells and a concurrent increase in the shared benefits, which accrue to both producers and cheats. Although PQS can be a beneficial signalling molecule forP. aeruginosa, our data suggests that it can also render a siderophore-producing population vulnerable to competition from cheating strains. More generally our results indicate that the production of one social trait can indirectly affect the costs and benefits of another social trait.

scholarly journals Indole Reverses Intrinsic Antibiotic Resistance by Activating a Novel Dual-Function Importer

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Yan Wang ◽  
Tian Tian ◽  
Jingjing Zhang ◽  
Xin Jin ◽  
Huan Yue ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Bacterial Species ◽  
Signaling Molecules ◽  
Dual Function ◽  
Vitamin B ◽  
Signal Molecule ◽  
Dynamic Regulation ◽  
Bacterial Antibiotic Resistance ◽  
Dependent Behavior

ABSTRACT Bacterial antibiotic resistance modulation by small signaling molecules is an emerging mechanism that has been increasingly reported in recent years. Several studies indicate that indole, an interkingdom signaling molecule, increases bacterial antibiotic resistance. However, the mechanism through which indole reduces antibiotic resistance is largely unknown. In this study, we demonstrated a novel mechanism for indole-mediated reversal of intrinsic antibiotic resistance in Lysobacter. This reversal was facilitated by a novel BtuD-associated dual-function importer that can transfer both vitamin B12 and antibiotics. Indole stimulated btuD overexpression and promoted efficient absorption of extracellular vitamin B12; meanwhile, the weak selectivity of the importer caused cells to take up excessive doses of antibiotics that resulted in cell death. Consistently, btuD deletion and G48Y/K49D substitution led to marked reductions in the uptake of both antibiotics and vitamin B12. This novel mechanism is common across multiple bacterial species, among which the Q-loop amino acid of BtuD proteins is Glu (E) instead of Gln (Q). Interestingly, the antibiotic resistance of Lysobacter spp. can be restored by another small quorum sensing signaling factor, 13-methyltetradecanoic acid, designated LeDSF, in response to bacterial population density. This work highlights the mechanisms underlying dynamic regulation of bacterial antibiotic resistance by small signaling molecules and suggests that the effectiveness of traditional antibiotics could be increased by coupling them with appropriate signaling molecules. IMPORTANCE Recently, signaling molecules were found to play a role in mediating antibiotic resistance. In this study, we demonstrated that indole reversed the intrinsic antibiotic resistance (IRAR) of multiple bacterial species by promoting the expression of a novel dual-function importer. In addition, population-dependent behavior induced by 13-methyltetradecanoic acid, a quorum sensing signal molecule designated LeDSF, was involved in the IRAR process. This study highlights the dynamic regulation of bacterial antibiotic resistance by small signaling molecules and provides direction for new therapeutic strategies using traditional antibiotics in combination with signaling molecules.

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 The Role of luxS in the Fire Blight Pathogen Erwinia amylovora Is Limited to Metabolism and Does Not Involve Quorum Sensing

2007 ◽  
Vol 20 (10) ◽  
pp. 1284-1297 ◽  
Author(s):  
Fabio Rezzonico ◽  
Brion Duffy
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Fire Blight ◽  
Erwinia Amylovora ◽  
Mutational Analysis ◽  
Pome Fruit ◽  
Autoinducer 2 ◽  
Metabolic Genes ◽  
Metabolic Role

Erwinia amylovora is a gram-negative phytopathogen that causes fire blight of pome fruit and related members of the family Rosaceae. We sequenced the putative autoinducer-2 (AI-2) synthase gene luxS from E. amylovora. Diversity analysis indicated that this gene is extremely conserved among E. amylovora strains. Quorum sensing mediated by LuxS has been implicated in coordinated gene expression, growth, and virulence in other enterobacteria; however, our evidence suggests this is not the function in E. amylovora. Mutational analysis pointed to a role in colonization of apple blossoms, the primary infection court for fire blight, although little if any role in virulence on apple shoots and pear fruit was observed. Expression of key virulence genes hrpL and dspA/E was reduced in mutants of two E. amylovora strains. Stronger effects on gene expression were observed for metabolic genes involved in the activated methyl cycle with mutants having greater levels of expression. No quorum-sensing effect was observed in co-culture experiments with wild-type and mutant strains either in vitro or in apple blossoms. Known receptors essential for AI-2 quorum sensing, the LuxPQ sensor kinase or the Lsr ABC-transporter, are absent in E. amylovora, further suggesting a primarily metabolic role for luxS in this bacterium.

scholarly journals Regulation of rpoS Gene Expression in Pseudomonas: Involvement of a TetR Family Regulator

2001 ◽  
Vol 183 (12) ◽  
pp. 3712-3720 ◽  
Author(s):  
Milan Kojic ◽  
Vittorio Venturi
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Quorum Sensing ◽  
Stationary Phase ◽  
Cell Density ◽  
Promoter Activity ◽  
Regulatory Protein ◽  
Insertion Mutant ◽  
Regulatory Cascade ◽  
A Cell

ABSTRACT The rpoS gene encodes the sigma factor which was identified in several gram-negative bacteria as a central regulator during stationary phase. rpoS gene regulation is known to respond to cell density, showing higher expression in stationary phase. For Pseudomonas aeruginosa, it has been demonstrated that the cell-density-dependent regulation response known as quorum sensing interacts with this regulatory response. Using therpoS promoter of P. putida, we identified a genomic Tn5 insertion mutant of P. putida which showed a 90% decrease in rpoSpromoter activity, resulting in less RpoS being present in a cell at stationary phase. Molecular analysis revealed that this mutant carried a Tn5 insertion in a gene, designatedpsrA (Pseudomonas sigma regulator), which codes for a protein (PsrA) of 26.3 kDa. PsrA contains a helix-turn-helix motif typical of DNA binding proteins and belongs to the TetR family of bacterial regulators. The homolog of thepsrA gene was identified in P. aeruginosa; the protein showed 90% identity to PsrA ofP. putida. ApsrA::Tn5 insertion mutant ofP. aeruginosa was constructed. In bothPseudomonas species, psrA was genetically linked to the SOS lexA repressor gene. Similar to what was observed for P. putida, a psrA null mutant of P. aeruginosa also showed a 90% reduction inrpoS promoter activity; both mutants could be complemented for rpoS promoter activity when thepsrA gene was provided in trans.psrA mutants of both Pseudomonas species lost the ability to induce rpoS expression at stationary phase, but they retained the ability to produce quorum-sensing autoinducer molecules. PsrA was demonstrated to negatively regulatepsrA gene expression in Pseudomonas and in Escherichia coli as well as to be capable of activating the rpoS promoter in E. coli. Our data suggest that PsrA is an important regulatory protein ofPseudomonas spp. involved in the regulatory cascade controlling rpoS gene regulation in response to cell density.

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