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PubMed2006

Involvement of quorum sensing and RpoS in rice seedling blight caused by Burkholderia plantarii.

Burkholderia plantarii is a plant pathogen responsible for causing rice seedling blight. The molecular mechanisms responsible for this pathogenicity are currently unknown. In this study, we report the identification and characterization of N-acyl homoserine lactone quorum sensing and the stationary phase RpoS sigma factor of B. plantarii. Both global regulatory systems are involved in causing rice seedling blight. This is the first report of gene regulators of B. plantarii implicated in the disease.

4-Butyrolactone↗

PubMed2005

Systems analysis of a quorum sensing network: design constraints imposed by the functional requirements, network topology and kinetic constants.

Understanding the relationship between the structural organization of intracellular decision networks and the observable phenotypes they control is one of the exigent problems of modern systems biology. Here we perform a systems analysis of a prototypic quorum sensing network whose operation allows bacterial populations to activate certain patterns of gene expression cooperatively. We apply structural perturbations to the model and analyze the resulting changes in the network behavior with the aim to identify the contribution of individual network elements to the functional fitness of the whole network. Specifically, we demonstrate the importance of the dimerization of the transcription factor and the presence of the auxiliary positive feedback loop on the switch-like behavior of the network and the stability of its "on" and "off" states under the influence of molecular noise.

Bacterial Proteins↗

PubMed2004

N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing.

A series of 11 new analogues of N-acylhomoserine lactones in which the carboxamide bond was replaced by a sulfonamide one, has been synthesised. These compounds were evaluated for their ability to competitively inhibit the action of 3-oxohexanoyl-L-homoserine lactone, the natural ligand of the quorum sensing transcriptional regulator LuxR, which in turn activates expression of bioluminescence in the model bacterium Vibrio fischeri. Several compounds were found to display antagonist activity. Molecular modeling suggests that the latter prevent a cascade of structural rearrangements necessary for the formation of the active LuxR dimer.

4-Butyrolactone↗

PubMed2002

Two opines control conjugal transfer of an Agrobacterium plasmid by regulating expression of separate copies of the quorum-sensing activator gene traR.

Conjugal transfer of Ti plasmids from Agrobacterium spp. is controlled by a hierarchical regulatory system designed to sense two environmental cues. One signal, a subset of the opines produced by crown gall tumors initiated on plants by the pathogen, serves to induce production of the second, an acyl-homoserine lactone quorum-sensing signal, the quormone, produced by the bacterium itself. This second signal activates TraR, and this transcriptional activator induces expression of the tra regulon. Opines control transfer because the traR gene is a member of an operon the expression of which is regulated by the conjugal opine. Among the Ti plasmid systems studied to date, only one of the two or more opine families produced by the associated tumor induces transfer. However, two chemically dissimilar opines, nopaline and agrocinopines A and B, induce transfer of the opine catabolic plasmid pAtK84b found in the nonpathogenic Agrobacterium radiobacter isolate K84. In this study we showed that this plasmid contains two copies of traR, and each is associated with a different opine-regulated operon. One copy, traR(noc), is the last gene of the nox operon and was induced by nopaline but not by agrocinopines A and B. Mutating traR(noc) abolished induction of transfer by nopaline but not by the agrocinopines. A mutation in ocd, an upstream gene of the nox operon, abolished utilization of nopaline and also induction of transfer by this opine. The second copy, traR(acc), is located in an operon of four genes and was induced by agrocinopines A and B but not by nopaline. Genetic analysis indicated that this gene is required for induction of transfer by agrocinopines A and B but not by nopaline. pAtK84b with mutations in both traR genes was not induced for transfer by either opine. However, expression of a traR gene in trans to this plasmid resulted in opine-independent transfer. The association of traR(noc) with nox is unique, but the operon containing traR(acc) is related to the arc operons of pTiC58 and pTiChry5, two Ti plasmids inducible for transfer by agrocinopines A-B and C-D, respectively. We conclude that pAtK84b codes for two independently functioning copies of traR, each regulated by a different opine, thus accounting for the activation of the transfer system of this plasmid by the two opine types.

Arginine↗

PubMed2005

Comparative analysis of two classes of quorum-sensing signaling systems that control production of extracellular proteins and secondary metabolites in Erwinia carotovora subspecies.

In Erwinia carotovora subspecies, N-acyl homoserine lactone (AHL) controls the expression of various traits, including extracellular enzyme/protein production and pathogenicity. We report here that E. carotovora subspecies possess two classes of quorum-sensing signaling systems defined by the nature of the major AHL analog produced as well as structural and functional characteristics of AHL synthase (AhlI) and AHL receptor (ExpR). Class I strains represented by E. carotovora subsp. atroseptica strain Eca12 and E. carotovora subsp. carotovora strains EC153 and SCC3193 produce 3-oxo-C8-HL (N-3-oxooctanoyl-l-homoserine lactone) as the major AHL analog as well as low but detectable levels of 3-oxo-C6-HL (N-3-oxohexanoyl-l-homoserine lactone). In contrast, the members of class II (i.e., E. carotovora subsp. betavasculorum strain Ecb168 and E. carotovora subsp. carotovora strains Ecc71 and SCRI193) produce 3-oxo-C6-HL as the major analog. ExpR species of both classes activate rsmA (Rsm, repressor of secondary metabolites) transcription and bind rsmA DNA. Gel mobility shift assays with maltose-binding protein (MBP)-ExpR(71) and MBP-ExpR(153) fusion proteins show that both bind a 20-mer sequence present in rsmA. The two ExpR functions (i.e., expR-mediated activation of rsmA expression and ExpR binding with rsmA DNA) are inhibited by AHL. The AHL effects are remarkably specific in that expR effect of EC153, a strain belonging to class I, is counteracted by 3-oxo-C8-HL but not by 3-oxo-C6-HL. Conversely, the expR effect of Ecc71, a strain belonging to class II, is neutralized by 3-oxo-C6-HL but not by 3-oxo-C8-HL. The AHL responses correlated with expR-mediated inhibition of exoprotein and secondary metabolite production.

4-Butyrolactone↗

PubMedDate not supplied

Modeling rhl quorum-sensing regulation on rhamnolipid production by Pseudomonas aeruginosa.

The effect of autoinducer PAI2 on rhamnolipid (RL) production by Pseudomonas aeruginosa was evaluated using an rhlI null mutant of PAO1 added with PAI2 at various concentrations. A model has also been developed to describe the production kinetics regulated by the rhl quorum-sensing system in three steps: First, PAI2 combines with RhlR protein. Second, the activated complex RhlR:PAI2 triggers the transcription (and expression) of the rhlAB operon that encodes for rhamnosyltransferase. Finally, the enzyme catalyzes the RL synthesis. The model describes fairly well the experimental results/profiles from three different studies (this and two others reported in the literature). The overall picture predicted by the model is as follows: The induced enzyme synthesis proceeds at the highest rate following PAI2 addition. The rate decreases with time as the autoinducer is degraded. The enzyme concentration nonetheless continues to increase until reaching the plateau at the exhaustion of autoinducer. Higher added PAI2 concentrations thus give not only higher initial enzyme synthesis rates but also longer induced synthesis. As the enzyme concentration increases with time, the RL production rate also increases, resulting in an accelerated rise in RL concentrations initially. The increase in RL concentrations becomes linear at the exhaustion of PAI2. The best-fit model parameters obtained also provided important insights. To complex half of the intracellular RhlR proteins would require 1.61 microM PAI2, about half of the PAI2 concentration obtained in the stationary-phase culture of wild-type PAO1. On the other hand, to activate the rhamnosyltransferase synthesis at half of its maximum rate would require the binding of 39% of RhlR with PAI2. The maximum RL production rate of the culture was found to be 0.042 g/L.h, and the fully induced culture would require at least 1.61 h to synthesize the enzyme to the necessary level for producing RL at half of the maximum rate.

Aldose-Ketose Isomerases↗

PubMed1997

Quorum sensing in Vibrio anguillarum: characterization of the vanI/vanR locus and identification of the autoinducer N-(3-oxodecanoyl)-L-homoserine lactone.

Certain gram-negative pathogens are known to control virulence gene expression through cell-cell communication via small diffusible signal molecules termed autoinducers. This intercellular signal transduction mechanism termed quorum sensing depends on the interaction of an N-acylhomoserine lactone (AHL) auto-inducer molecule with a receptor protein belonging to the LuxR family of positive transcriptional activators. Vibrio anguillarum is a gram-negative pathogen capable of causing a terminal hemorrhagic septicemia known as vibriosis in fish such as rainbow trout. In this study, we sought to determine whether V. anguillarum employs AHLs to regulate virulence gene expression. Spent V. anguillarum culture supernatants stimulated bioluminescence in a recombinant lux-based Escherichia coli AHL biosensor strain, whereas they both stimulated and inhibited AHL-mediated violacein pigment production in Chromobacterium violaceum. This finding suggested that V. anguillarum may produce multiple AHL signal molecules. Using high-performance liquid chromatography and high-resolution tandem mass spectrometry, we identified the major V. anguillarum AHL as N-(3-oxodecanoyl)-L-homoserine lactone (ODHL), a structure which was unequivocally confirmed by chemical synthesis. The gene (vanI) responsible for ODHL synthesis was cloned and sequenced and shown to belong to the LuxI family of putative AHL synthases. Further sequencing downstream of vanI revealed a second gene (vanR) related to the LuxR family of transcriptional activators. Although deletion of vanI abolished ODHL synthesis, no reduction of either metalloprotease production or virulence in a fish infection model was observed. However, the vanI mutant remained capable of weakly activating both bioluminescence and violacein in the E. coli and C. violaceum biosensors, respectively, indicating the existence of additional layers of AHL-mediated regulatory complexity.

Amino Acid Sequence↗

PubMed2002

LuxS-mediated quorum sensing in Borrelia burgdorferi, the lyme disease spirochete.

The establishment of Borrelia burgdorferi infection involves numerous interactions between the bacteria and a variety of vertebrate host and arthropod vector tissues. This complex process requires regulated synthesis of many bacterial proteins. We now demonstrate that these spirochetes utilize a LuxS/autoinducer-2 (AI-2)-based quorum-sensing mechanism to regulate protein expression, the first system of cell-cell communication to be described in a spirochete. The luxS gene of B. burgdorferi was identified and demonstrated to encode a functional enzyme by complementation of an Escherichia coli luxS mutant. Cultured B. burgdorferi responded to AI-2 by altering the expression levels of a large number of proteins, including the complement regulator factor H-binding Erp proteins. Through this mechanism, a population of Lyme disease spirochetes may synchronize production of specific proteins needed for infection processes.

Amino Acid Sequence↗

PubMed2001

Amino acid residues in LuxR critical for its mechanism of transcriptional activation during quorum sensing in Vibrio fischeri.

PCR-based site-directed mutagenesis has been used to generate 38 alanine-substitution mutations in the C-terminal 41 amino acid residues of LuxR. This region plays a critical role in the mechanism of LuxR-dependent transcriptional activation of the Vibrio fischeri lux operon during quorum sensing. The ability of the variant forms of LuxR to activate transcription of the lux operon was examined by using in vivo assays in recombinant Escherichia coli. Eight recombinant strains produced luciferase at levels less than 50% of that of a strain expressing wild-type LuxR. Western immunoblotting analysis verified that the altered forms of LuxR were expressed at levels equivalent to those of the wild type. An in vivo DNA binding-repression assay in recombinant E. coli was subsequently used to measure the ability of the variant forms of LuxR to bind to the lux box, the binding site of LuxR at the lux operon promoter. All eight LuxR variants found to affect cellular luciferase levels were unable to bind to the lux box. An additional 11 constructs that had no effect on cellular luciferase levels were also found to exhibit a defect in DNA binding. None of the alanine substitutions in LuxR affected activation of transcription of the lux operon without also affecting DNA binding. These results support the conclusion that the C-terminal 41 amino acids of LuxR are important for DNA recognition and binding of the lux box rather than positive control of the process of transcription initiation.

Alanine↗

PubMed2006

Quorum sensing in the genus Burkholderia.

The genus Burkholderia contains over 30 species, many of which are important human pathogens. In addition to the primary pathogens Burkholderia pseudomallei and Burkholderia mallei, several species have emerged as opportunistic pathogens in persons suffering from cystic fibrosis (CF) and immunocompromised individuals. All Burkholderia species investigated so far employ quorum-sensing (QS) systems that rely on N-acyl-homoserine lactone (AHL) signal molecules to express certain phenotypic traits in a population density-dependent manner. Whilst many Burkholderia strains only contain the CepI/CepR QS system, which relies on C8-HSL, some strains, in particular isolates of B. pseudomallei and B. mallei, harbour multiple LuxI/LuxR homologues and produce numerous AHL signal molecules. Evidence has accumulated over the past few years that the QS systems operating in Burkholderia are crucial for full virulence in various animal models. However, only few QS-regulated functions required for virulence in the different infection models have so far been identified. Given the essential role of QS in the expression of pathogenic traits in Burkholderia these regulatory systems represent attractive targets for the development of novel therapeutics.

4-Butyrolactone↗

PubMed2002

Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets.

Recent evidence indicates that Pseudomonas aeruginosa residing as biofilms in airway mucus of cystic fibrosis (CF) patients is undergoing anaerobic metabolism, a form of growth requiring gene products that are not utilized during aerobic growth. The outer membrane protein, OprF, and the rhl quorum sensing circuit are two previously unrecognized cellular factors that are required for optimal anaerobic biofilm viability. Without OprF, bacteria grow extremely poorly because they lack nitrite reductase activity while lacking rhlR or rhlI forces bacteria to undergo metabolic suicide by overproduction of nitric oxide. Furthermore, anaerobic growth favors maintenance of the mucoid, alginate-overproducing phenotype. Thus, with increasing age of CF patients, mucoid populations predominate, indicating that anaerobic bacteria reside in the inspissated airway mucus. Because many frontline antibiotics used in the treatment of CF airway disease are either ineffective or show reduced efficacy during anaerobic conditions, we propose development of new drugs to combat anaerobic metabolism by P. aeruginosa for more effective treatment of chronic CF lung infections.

Alginates↗

PubMed2003

Use of the quorum-sensing inhibitor RNAIII-inhibiting peptide to prevent biofilm formation in vivo by drug-resistant Staphylococcus epidermidis.

Staphylococcus epidermidis is a frequent cause of infections associated with foreign bodies and indwelling medical devices. The bacteria are capable of surviving antibiotic treatment through encapsulation into biofilms. RNAIII-inhibiting peptide (RIP) is a heptapeptide that inhibits S. aureus pathogenesis by disrupting quorum-sensing mechanisms. In this study, RIP inhibited drug-resistant S. epidermidis biofilm formation through a mechanism similar to that evidenced for S. aureus. RIP is synergistic with antibiotics in eliminating 100% of graft-associated in vivo S. epidermidis infections, which suggests that RIP may be used to coat medical devices to prevent staphylococcal infections. Disruption of cell-cell communication can prevent infections associated with antibiotic-resistant strains.

Adaptor Proteins, Signal Transducing↗

PubMed2000

hexA of Erwinia carotovora ssp. carotovora strain Ecc71 negatively regulates production of RpoS and rsmB RNA, a global regulator of extracellular proteins, plant virulence and the quorum-sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone.

The soft-rotting bacterium, Erwinia carotovora ssp. carotovora (E. c. carotovora), produces an array of extracellular enzymes (= exoenzymes), including pectate lyase (Pel), polygalacturonase (Peh), cellulase (Cel) and protease (Prt), as well as HarpinEcc, the elicitor of hypersensitive reaction (HR). The production of these exoenzymes and HarpinEcc responds to plant products and the quorum-sensing signal [N-(3-oxohexanoyl)-L-homoserine lactone; OHL] and is subject to both transcriptional and post-transcriptional regulation. hexA of E. c. carotovora strain Ecc71 (hereafter hexA71), like that of another E. c. carotovora strain, negatively controls the production of exoenzymes, OHL and virulence in E. c. carotovora strain Ecc71. In addition to exoenzymes, HexA71 negatively regulates the expression of hrpNEcc, the structural gene for HarpinEcc. Exoenzyme overproduction is abolished by OHL deficiency in a HexA- and Ohll- double mutant, indicating that HexA and OHL are components of a common regulatory pathway controlling exoenzyme production. HexA71 negatively affects RpoS, as the levels of this alternative sigma factor are higher in the HexA- mutant than in the HexA+ strain. However, a HexA- and RpoS double mutant produces higher levels of exoenzymes and transcripts of pel-1, peh-1 and celVgenes than the HexA- and RpoS+ parent. Thus, the elevated levels of RpoS protein in the HexA- mutant do not account for exoenzyme overproduction. The following evidence associates for the first time the phenotypic changes in the HexA mutant to overproduction of rsmB RNA, a global regulator of exoenzymes, HarpinEcc, OHL and secondary metabolites. Analyses of rsmB transcripts and expression of an rsmB-lacZoperon fusion in E. c. carotovora strain Ecc71 revealed that HexA71 negatively regulates transcription of rsmB. Multiple copies of hexA71+ DNA suppress various phenotypes, including exoenzyme production in E. c. carotovora strain Ecc71, and concomitantly inhibit the production of rsmB, pel-1, peh-1, celV and hrpNEcc transcripts. Multiple copies of rsmB+ DNA, on the other hand, stimulate exoenzyme production by relieving the negative effects of a chromosomal copy of hexA+. The occurrence of hexA homologues and the negative effect of the dosage of hexA71 DNA on rsmB transcripts were also detected in other E. c. carotovora strains as well as Erwinia carotovora atroseptica and Erwinia carotovora betavasculorum. Extrapolating from the findings with LrhA, the Escherichia coli homologue of HexA, and the presence of sprE homologues in E. carotovora subspecies, we propose that HexA71 controls several regulatory pathways in E. carotovora including rsmB transcription and the production of SprEEcc which, in turn, affects RpoS levels. A model is presented that integrates the findings presented here and our current knowledge of the major regulatory network that controls exoprotein production in soft-rotting Erwinia carotovora subspecies.

4-Butyrolactone↗

PubMed2005

Biofilm formation of Pseudomonas putida IsoF: the role of quorum sensing as assessed by proteomics.

Pseudomonas putida strains are frequently isolated from the rhizosphere of plants and many strains promote plant-growth, exhibit antagonistic activities against plant pathogens and have the capacity to degrade pollutants. Factors that appear to contribute to the rhizosphere fitness are the ability of the organism to form biofilms and the utilization of cell-to-cell-communication systems (quorum sensing, QS) to co-ordinate the expression of certain phenotypes in a cell density dependent manner. Recently, the ppu QS locus of the tomato rhizosphere isolate P. putida Iso F was characterized and an isogenic QS-negative ppuI mutant P. putida F117 was generated. In the present study we investigated the impact of QS and biofilm formation on the protein profile of surface-associated proteins of P. putida IsoF. This was accomplished by comparative proteome analyses of the P. putida wild type IsoF and the QS-deficient mutant F117 grown either in planktonic cultures or in 60 h old mature biofilms. Differentially expressed proteins were identified by peptide mass fingerprinting and database search in the completed P. putida KT2440 genome sequence. The sessile life style affected 129 out of 496 surface proteins, suggesting that a significant fraction of the bacterial genome is involved in biofilm physiology. In surface-attached cells 53 out of 484 protein spots were controlled by the QS system, emphasizing its importance as global regulator of gene expression in P. putida IsoF. Most interestingly, the impact of QS was dependent on whether cells were grown on a surface or in suspension; about 50% of the QS-controlled proteins identified in planktonic cultures were found to be oppositely regulated when the cells were grown as biofilms. Fifty-seven percent of all identified surface-controlled proteins were also regulated by the ppu QS system. In conclusion, our data provide strong evidence that the set of QS-regulated proteins overlaps substantially with the set of proteins differentially expressed in sessile cells.

Bacterial Proteins↗

PubMed2005

Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector.

With the widespread appearance of antibiotic-resistant bacteria, there is an increasing demand for novel strategies to control infectious diseases. Furthermore, it has become apparent that the bacterial life style also contributes significantly to this problem. Bacteria living in the biofilm mode of growth tolerate conventional antimicrobial treatments. The discovery that many bacteria use quorum-sensing (QS) systems to coordinate virulence and biofilm development has pointed out a new, promising target for antimicrobial drugs. We constructed a collection of screening systems, QS inhibitor (QSI) selectors, which enabled us to identify a number of novel QSIs among natural and synthetic compound libraries. The two most active were garlic extract and 4-nitro-pyridine-N-oxide (4-NPO). GeneChip-based transcriptome analysis revealed that garlic extract and 4-NPO had specificity for QS-controlled virulence genes in Pseudomonas aeruginosa. These two QSIs also significantly reduced P. aeruginosa biofilm tolerance to tobramycin treatment as well as virulence in a Caenorhabditis elegans pathogenesis model.

4-Butyrolactone↗

PubMedDate not supplied

Regulation of competence for genetic transformation in Streptococcus pneumoniae: a link between quorum sensing and DNA processing genes.

Competence for genetic transformation in pneumococcus depends on the coordinated functioning of a dispersed regulon responsible for production of proteins active in DNA binding, uptake, and recombination. This regulon is characterized by a shared noncanonical promoter consensus, TACGAATA, and is capable of 100-fold expression modulations. This review discusses recent evidence that its regulation depends on a novel sigma factor, itself controlled by an autostimulatory quorum sensing system that acts through an extracellular peptide signal.

Bacterial Proteins↗

PubMed1998

The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone has immunomodulatory activity.

Diverse gram-negative bacterial cells communicate with each other by using diffusible N-acyl homoserine lactone (AHL) signal molecules to coordinate gene expression with cell population density. Accumulation of AHLs above a threshold concentration renders the population "quorate," and the appropriate target gene is activated. In pathogenic bacteria, such as Pseudomonas aeruginosa, AHL-mediated quorum sensing is involved in the regulation of multiple virulence determinants. We therefore sought to determine whether the immune system is capable of responding to these bacterial signal molecules. Consequently the immunomodulatory properties of the AHLs N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) were evaluated in murine and human leukocyte immunoassays in vitro. OdDHL, but not OHHL, inhibited lymphocyte proliferation and tumor necrosis factor alpha production by lipopolysaccharide-stimulated macrophages. Furthermore, OdDHL simultaneously and potently down-regulated the production of IL-12, a Th-1-supportive cytokine. At high concentrations (>7 x 10(-5) M) OdDHL inhibited antibody production by keyhole limpet hemocyanin-stimulated spleen cells, but at lower concentrations (<7 x 10(-5) M), antibody production was stimulated, apparently by increasing the proportion of the immunoglobulin G1 (IgG1) isotype. OdDHL also promoted IgE production by interleukin-4-stimulated human peripheral blood mononuclear cells. These data indicate that OdDHL may influence the Th-1-Th-2 balance in the infected host and suggest that, in addition to regulating the expression of virulence determinants, OdDHL may contribute to the pathogenesis of P. aeruginosa infections by functioning as a virulence determinant per se.

4-Butyrolactone↗

PubMed2005

Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent.

The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant to otherwise lethal doses of antibiotics and are protected from bactericidal activity of polymorphonuclear leukocytes (PMNs). P. aeruginosa controls the expression of many of its virulence factors by means of a cell-cell communication system termed quorum sensing (QS). In the present report it is demonstrated that biofilm bacteria in which QS is blocked either by mutation or by administration of QS inhibitory drugs are sensitive to treatment with tobramycin and H2O2, and are readily phagocytosed by PMNs, in contrast to bacteria with functional QS systems. In contrast to the wild-type, QS-deficient biofilms led to an immediate respiratory-burst activation of the PMNs in vitro. In vivo QS-deficient mutants provoked a higher degree of inflammation. It is suggested that quorum signals and QS-inhibitory drugs play direct and opposite roles in this process. Consequently, the faster and highly efficient clearance of QS-deficient bacteria in vivo is probably a two-sided phenomenon: down regulation of virulence and activation of the innate immune system. These data also suggest that a combination of the action of PMNs and QS inhibitors along with conventional antibiotics would eliminate the biofilm-forming bacteria before a chronic infection is established.

Animals↗