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PubMed2006

Functional characterization of a three-component regulatory system involved in quorum sensing-based regulation of peptide antibiotic production in Carnobacterium maltaromaticum.

BACKGROUND: Quorum sensing is a form of cell-to-cell communication that allows bacteria to control a wide range of physiological processes in a population density-dependent manner. Production of peptide antibiotics is one of the processes regulated by quorum sensing in several species of Gram-positive bacteria, including strains of Carnobacterium maltaromaticum. This bacterium and its peptide antibiotics are of interest due to their potential applications in food preservation. The molecular bases of the quorum sensing phenomenon controlling peptide antibiotic production in C. maltaromaticum remain poorly understood. The present study was aimed at gaining a deeper insight into the molecular mechanism involved in quorum sensing-mediated regulation of peptide antibiotic (bacteriocin) production by C. maltaromaticum. We report the functional analyses of the CS (autoinducer)-CbnK (histidine protein kinase)-CbnR (response regulator) three-component regulatory system and the three regulated promoters involved in peptide antibiotic production in C. maltaromaticum LV17B. RESULTS: CS-CbnK-CbnR system-dependent activation of carnobacterial promoters was demonstrated in both homologous and heterologous hosts using a two-plasmid system with a beta-glucuronidase (GusA) reporter read-out. The results of our analyses support a model in which the CbnK-CbnR two-component signal transduction system is necessary and sufficient to transduce the signal of the peptide autoinducer CS into the activation of the promoters that drive the expression of the genes required for production of the carnobacterial peptide antibiotics and the immunity proteins that protect the producer bacterium. CONCLUSIONS: The CS-CbnK-CbnR triad forms a three-component regulatory system by which production of peptide antibiotics by C. maltaromaticum LV17B is controlled in a population density-dependent (or cell proximity-dependent) manner. This regulatory mechanism would permit the bacterial population to synchronize the production of peptide antibiotics and immunity proteins. Such a population-wide action would afford a substantial peptide antibiotic production burst that could increase the ability of the bacterium to inhibit susceptible bacterial competitors. Finally, our CS-CbnK-CbnR-based two-plasmid expression system represents a suitable genetic tool for undertaking structure-function relationship analyses to map the amino acid residues in the components of the CS-CbnK-CbnR system that are required for biological activity. This plasmid system also has potential as a starting point for developing alternative vectors for controlled gene expression in C. maltaromaticum, Lactococcus lactis, and related lactic acid bacteria.

Anti-Bacterial Agents↗
PubMed2004

Quorum sensing-controlled biofilm development in Serratia liquefaciens MG1.

Serratia liquefaciens MG1 contains an N-acylhomoserine lactone-mediated quorum-sensing system that is known to regulate swarming motility colonization. In this study, we describe for S. liquefaciens MG1 the development of a novel biofilm consisting of cell aggregates and differentiated cell types, such as cell chains and long filamentous cells. Furthermore, quorum sensing is shown to be crucial for normal biofilm development and for elaborate differentiation. A mutant of S. liquefaciens MG1 that was incapable of synthesizing extracellular signal formed a thin and nonmature biofilm lacking cell aggregates and differentiated cell chains. Signal-based complementation of this mutant resulted in a biofilm with the wild-type architecture. Two quorum-sensing-regulated genes (bsmA and bsmB) involved in biofilm development were identified, and we propose that these genes are engaged in fine-tuning the formation of cell aggregates at a specific point in biofilm development.

4-Butyrolactone↗
PubMed2005

Carbapenem antibiotic biosynthesis in Erwinia carotovora is regulated by physiological and genetic factors modulating the quorum sensing-dependent control pathway.

Erwinia carotovora produces the beta-lactam antibiotic, carbapenem, in response to a quorum sensing signalling molecule, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). We have mapped the OHHL-dependent promoter upstream of the first of the biosynthetic genes, carA. We have also analysed the effect on this promoter of the known genetic regulators of carbapenem expression, carR, carI (encoding homologues of LuxR and LuxI respectively) and hor (encoding a SlyA/MarR-like transcriptional regulator). We describe a previously unknown promoter located within the carA-H operon. This promoter does not respond to CarR and is required for quorum sensing-independent expression of the carbapenem resistance determinants encoded by the carFG genes. We have mapped the carR, carI and hor transcription start points, shown that CarR is positively autoregulated in the presence of OHHL, and have demonstrated negative feedback affecting transcription of carI. In addition, various environmental and physiological factors were shown to impinge on the transcription of the car biosynthetic genes. The nature of the carbon source and the temperature of growth influence carbapenem production by modulating the level of the OHHL signalling molecule, and thereby physiologically fine-tune the quorum sensing regulatory system.

4-Butyrolactone↗
PubMed2006

Quorum sensing-disrupting brominated furanones protect the gnotobiotic brine shrimp Artemia franciscana from pathogenic Vibrio harveyi, Vibrio campbellii, and Vibrio parahaemolyticus isolates.

Autoinducer 2 (AI-2) quorum sensing was shown before to regulate the virulence of Vibrio harveyi towards the brine shrimp Artemia franciscana. In this study, several different pathogenic V. harveyi, Vibrio campbellii, and Vibrio parahaemolyticus isolates were shown to produce AI-2. Furthermore, disruption of AI-2 quorum sensing by a natural and a synthetic brominated furanone protected gnotobiotic Artemia from the pathogenic isolates in in vivo challenge tests.

Animals↗
PubMed2002

Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa.

A set of 30 mutants exhibiting reduced production of the phenazine poison pyocyanin were isolated following transposon mutagenesis of Pseudomonas aeruginosa PAO1. The mutants could be subdivided into those with defects in the primary phenazine biosynthetic pathway and those with more pleiotropic defects. The largest set of pleiotropic mutations blocked the production of the extracellular Pseudomonas quinolone signal (PQS), a molecule required for the synthesis of secondary metabolites and extracellular enzymes. Most of these pqs mutations affected genes which appear to encode PQS biosynthetic functions, although a transcriptional regulator and an apparent response effector were also represented. Two of the genes required for PQS synthesis (phnA and phnB) had previously been assumed to encode phenazine biosynthetic functions. The transcription of one of the genes required for PQS synthesis (PA2587/pqsH) was regulated by the LasI/R quorum-sensing system, thereby linking quorum sensing and PQS regulation. Others of the pleiotropic phenazine-minus mutations appear to inactivate novel components of the quorum-sensing regulatory network, including one regulator (np20) previously shown to be required for virulence in neutropenic mice.

Animals↗
PubMed2006

Does Pseudomonas aeruginosa use intercellular signalling to build biofilm communities?

Pseudomonas aeruginosa is a Gram-negative bacterial species that causes several opportunistic human infections. This organism is also found in the environment, where it is renowned (like other Pseudomonads) for its ability to use a wide variety of compounds as carbon and energy sources. It is a model species for studying group-related behaviour in bacteria. Two types of group behaviour it engages in are intercellular signalling, or quorum sensing, and the formation of surface-associated communities called biofilms. Both quorum sensing and biofilm formation are important in the pathogenesis of P. aeruginosa infections. Quorum sensing regulates the expression of several secreted virulence factors and quorum sensing mutant strains are attenuated for virulence in animal models. Biofilms have been implicated in chronic infections. Two examples are the chronic lung infections afflicting people suffering from cystic fibrosis and colonization of indwelling medical devices. This review will discuss quorum sensing and biofilm formation and studies that link these two processes.

Biofilms↗
PubMed2003

Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae.

Vibrio cholerae is the causative agent of the diarrheal disease cholera. By an incompletely understood developmental process, V. cholerae forms complex surface-associated communities called biofilms. Here we show that quorum sensing-deficient mutants of V. cholerae produce thicker biofilms than those formed by wild-type bacteria. Microarray analysis of biofilm-associated bacteria shows that expression of the Vibrio polysaccharide synthesis (vps) operons is enhanced in hapR mutants. CqsA, one of two known autoinducer synthases in V. cholerae, acts through HapR to repress vps gene expression. Vibrio biofilms are more acid resistant than planktonic cells. However, quorum sensing-deficient biofilms have lower colonization capacities than those of wild-type biofilms, suggesting that quorum sensing may promote cellular exit from the biofilm once the organisms have traversed the gastric acid barrier of the stomach. These results shed light on the relationships among biofilm development, quorum sensing, infectivity, and pathogenesis in V. cholerae.

Acyltransferases↗
PubMed2003

Mutation of luxS affects biofilm formation in Streptococcus mutans.

Quorum sensing is a bacterial mechanism for regulating gene expression in response to changes in population density. Many bacteria are capable of acyl-homoserine lactone-based or peptide-based intraspecies quorum sensing and luxS-dependent interspecies quorum sensing. While there is good evidence about the involvement of intraspecies quorum sensing in bacterial biofilm, little is known about the role of luxS in biofilm formation. In this study, we report for the first time that luxS-dependent quorum sensing is involved in biofilm formation of Streptococcus mutans. S. mutans is a major cariogenic bacterium in the multispecies bacterial biofilm commonly known as dental plaque. An ortholog of luxS for S. mutans was identified using the data available in the S. mutans genome project (http://www.genome.ou.edu/smutans.html). Using an assay developed for the detection of the LuxS-associated quorum sensing signal autoinducer 2 (AI-2), it was demonstrated that this ortholog was able to complement the luxS negative phenotype of Escherichia coli DH5alpha. It was also shown that AI-2 is indeed produced by S. mutans. AI-2 production is maximal during mid- to late-log growth in batch culture. Mutant strains devoid of the luxS gene were constructed and found to be defective in producing the AI-2 signal. There are also marked phenotypic differences between the wild type and the luxS mutants. Microscopic analysis of in vitro-grown biofilm structure revealed that the luxS mutant biofilms adopted a much more granular appearance, rather than the relatively smooth, confluent layer normally seen in the wild type. These results suggest that LuxS-dependent signal may play an important role in biofilm formation of S. mutans.

Amino Acid Sequence↗
PubMed1999

Quorum sensing-dependent regulation and blockade of exoprotease production in Aeromonas hydrophila.

In Aeromonas hydrophila, the ahyI gene encodes a protein responsible for the synthesis of the quorum sensing signal N-butanoyl-L-homoserine lactone (C4-HSL). Inactivation of the ahyI gene on the A. hydrophila chromosome abolishes C4-HSL production. The exoprotease activity of A. hydrophila consists of both serine protease and metalloprotease activities; in the ahyI-negative strain, both are substantially reduced but can be restored by the addition of exogenous C4-HSL. In contrast, mutation of the LuxR homolog AhyR results in the loss of both exoprotease activities, which cannot be restored by exogenous C4-HSL. Furthermore, a substantial reduction in the production of exoprotease by the ahyI+ parent strain is obtained by the addition of N-acylhomoserine lactone analogs that have acyl side chains of 10, 12, or 14 carbons. The inclusion of N-(3-oxododecanoyl)-L-homoserine lactone or N-(3-oxotetradecanoyl)-L-homoserine lactone at 10 microM in overnight cultures of A. hydrophila abolishes exoprotease production in azocasein assays and reduces the activity of all the exoprotease species seen in zymograms.

4-Butyrolactone↗
PubMed2005

Bacteroides species produce Vibrio harveyi autoinducer 2-related molecules.

Quorum sensing is a density-dependent gene regulation mechanism that has been described in many bacterial species in the last decades. Bacteria that use quorum sensing as part of their gene regulation circuits produce molecules called autoinducers that accumulate in the environment and activate target genes in a quorum-dependent way. Some specific clues led us to hypothesize that Bacteroides species can produce autoinducers and possess a quorum sensing system. First, Bacteroides are anaerobic bacteria that are frequently involved in polymicrobial infections. These infections often involve Pseudomonas aeruginosa and Staphylococcus aureus, two of the best understood examples of bacteria that employ quorum sensing systems as part of their pathogenesis. Also, studies have detected the presence of a quorum sensing gene involved in the production of autoinducers in Porphyromonas gingivalis, a species closely related to the Bacteroides genus. These and other evidences prompted us to investigate if Bacteroides strains could produce autoinducer molecules that could be detected by a Vibrio harveyi reporter system. In this paper, we show that supernatants of B. fragilis, B. vulgatus and B. distasonis strains are able to stimulate the V. harveyi quorum sensing system 2. Also, we were able to demonstrate that the stimulation detected is due to the production of autoinducer molecules and not the growth of reporter strains after addition of supernatant. Moreover, the phenomenon observed does not seem to represent the degradation of repressors possibly present in the culture medium used. We could also amplify bands from some of the strains tested using primers designed to the luxS gene of Escherichia coli. Altogether, our results show that B. fragilis, B. vulgatus and B. distasonis (but possibly some other species) can produce V. harveyi autoinducer 2-related molecules. However, the role of such molecules in the biology of these organisms remains unknown.

Journal Article↗
PubMed2006

Identification of a constitutively active variant of LuxO that affects production of HA/protease and biofilm development in a non-O1, non-O139 Vibrio cholerae O110.

Pathogenesis of Vibrio cholerae depends on the concerted action of numerous virulence factors that includes a secreted hemagglutinin (HA) protease. Recent studies have evidenced that the expression of these virulence factors as well as the genes responsible for biofilm development is subject to control by quorum sensing in this organism. At low cell density, LuxO, the pivotal regulator of quorum-sensing circuit, has been shown to be phosphorylated at aspartate-47. Working in concert with sigma-54, LuxO-P activates the downstream repressor, which turned out to be four sRNAs [Lenz, D.H., Mok, K.C., Lilley, B.N., Kulkarni, R.V., Wingreen, N.S., Bassler, B.L., 2004. The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118, 69-82]. Subsequently, these sRNAs form complex with sRNA chaperone, Hfq. The Hfq-sRNA complex causes the destabilization of hapR mRNA transcript. HapR is a positive regulator of hapA that encodes HA/protease. At high cell density, dephosphorylation of LuxO impairs its function to activate the expression of sRNA, which in turn promotes HapR expression and causes protease production. It has been demonstrated that conversion of aspartate to glutamate (D47E) renders the LuxO molecule active without being phosphorylated. This variant of LuxO is referred as constitutively active LuxO or con-LuxO [Freeman, J.A., Bassler, B.L., 1999. A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi. Mol Microbiol 31, 665-677]. Other than D47E, mutation at L104Q also develops con-LuxO [Vance, R.E., Zhu, J., Mekalanos, J.J., 2003. A constitutively active variant of the quorum-sensing regulator LuxO affects protease production and biofilm formation in Vibrio cholerae. Infect. Immun. 71, 2571-2576]. The purpose of this study was to investigate the cause of protease negative phenotype of a non-O1, non-O139 strain of V. cholerae O110. In the process of exploring the nature of the phenotype, a constitutively active variant of LuxO molecule was characterized which represses protease production and enhances biofilm formation by this strain. Unlike luxU, disruption of luxO restored the protease production, which showed the constitutively active nature of LuxO protein in this strain.

Amino Acid Sequence↗
PubMed2004

Inoculum size effect in dimorphic fungi: extracellular control of yeast-mycelium dimorphism in Ceratocystis ulmi.

We studied the inoculum size effect in Ceratocystis ulmi, the dimorphic fungus that causes Dutch elm disease. In a defined glucose-proline-salts medium, cells develop as budding yeasts when inoculated at > or = 10(6) spores per ml and as mycelia when inoculated at <10(6) spores per ml. The inoculum size effect was not influenced by inoculum spore type, age of the spores, temperature, pH, oxygen availability, trace metals, sulfur source, phosphorous source, or the concentration of glucose or proline. Similarly, it was not influenced by added adenosine, reducing agents, methyl donors, amino sugars, fatty acids, or carbon dioxide. Instead, growing cells excreted an unknown quorum-sensing factor that caused a morphological shift from mycelia to budding yeasts. This yeast-promoting effect is abolished if it is extracted with an organic solvent such as ethyl acetate. The quorum-sensing activity acquired by the organic solvent could be added back to fresh medium in a dose-dependent fashion. The quorum-sensing activity in C. ulmi spent medium was specific for C. ulmi and had no effect on the dimorphic fungus Candida albicans or the photomorphogenic fungus Penicillium isariaeforme. In addition, farnesol, the quorum-sensing molecule produced by C. albicans, did not inhibit mycelial development of C. ulmi when present at concentrations of up to 100 microM. We conclude that the inoculum size effect is a manifestation of a quorum-sensing system that is mediated by an excreted extracellular molecule, and we suggest that quorum sensing is a general phenomenon in dimorphic fungi.

Ascomycota↗
PubMed2006

Producing mechanism of an algicidal compound against red tide phytoplankton in a marine bacterium gamma-proteobacterium.

Strain MS-02-063, gamma-proteobacterium, isolated from a coast area of Nagasaki, Japan, produced a red pigment which belongs to prodigiosin members. This pigment, PG-L-1, showed potent algicidal activity against various red tide phytoplanktons in a concentration-dependent manner. An understanding of a mechanism of PG-L-1 production by this marine bacterium may yield important new insights and strategies for preventing blooms of harmful flagellate algae in natural marine environments. Therefore, we analyzed the mechanisms of PG-L-1 production. In our previous study, the pigment production by this marine bacterium was completely inhibited at 1.56 microg/ml of erythromycin or 3.13 microg/ml of chloramphenicol, while minimal inhibitory concentrations for cell growth of erythromycin and chloramphenicol against this bacterium were >100 and 25 microg/ml, respectively. It is interesting to note that the ability of the pigment production in erythromycin-treated bacterium recovered by an addition of homoserine lactone. In fact, the pigment production was inhibited by beta-cyclodextrin that inhibits autoinducer activities by a complex with N-acyl homoserine lactones. N-acyl homoserine lactones with autoinducer activities are ubiquitous bacterial signaling molecules that regulate gene expression in a cell density dependent process known as quorum sensing. Therefore, it was suggested that PG-L-1 produced by strain MS-02-063 is controlled by the homoserine lactone quorum sensing. It is speculated that this quorum sensing is involved in the production of algicidal agents of other marine bacteria. This bacterium and other algicidal bacteria might be concerned in regulating the blooms of harmful flagellate algae through the quorum sensing system.

Animals↗
PubMed2003

Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis.

There are two interrelated acyl-homoserine lactone quorum-sensing-signaling systems in Pseudomonas aeruginosa. These systems, the LasR-LasI system and the RhlR-RhlI system, are global regulators of gene expression. We performed a transcriptome analysis to identify quorum-sensing-controlled genes and to better understand quorum-sensing control of P. aeruginosa gene expression. We compared gene expression in a LasI-RhlI signal mutant grown with added signals to gene expression without added signals, and we compared a LasR-RhlR signal receptor mutant to its parent. In all, we identified 315 quorum-induced and 38 quorum-repressed genes, representing about 6% of the P. aeruginosa genome. The quorum-repressed genes were activated in the stationary phase in quorum-sensing mutants but were not activated in the parent strain. The analysis of quorum-induced genes suggests that the signal specificities are on a continuum and that the timing of gene expression is on a continuum (some genes are induced early in growth, most genes are induced at the transition from the logarithmic phase to the stationary phase, and some genes are induced during the stationary phase). In general, timing was not related to signal concentration. We suggest that the level of the signal receptor, LasR, is a critical trigger for quorum-activated gene expression. Acyl-homoserine lactone quorum sensing appears to be a system that allows ordered expression of hundreds of genes during P. aeruginosa growth in culture.

4-Butyrolactone↗
PubMed2001

Mapping stress-induced changes in autoinducer AI-2 production in chemostat-cultivated Escherichia coli K-12.

Numerous gram-negative bacteria employ a cell-to-cell signaling mechanism, termed quorum sensing, for controlling gene expression in response to population density. Recently, this phenomenon has been discovered in Escherichia coli, and while pathogenic E. coli utilize quorum sensing to regulate pathogenesis (i.e., expression of virulence genes), the role of quorum sensing in nonpathogenic E. coli is less clear, and in particular, there is no information regarding the role of quorum sensing during the overexpression of recombinant proteins. The production of autoinducer AI-2, a signaling molecule employed by E. coli for intercellular communication, was studied in E. coli W3110 chemostat cultures using a Vibrio harveyi AI-2 reporter assay (M. G. Surrette and B. L. Bassler, Proc. Natl. Acad. Sci. USA 95:7046-7050, 1998). Chemostat cultures enabled a study of AI-2 regulation through steady-state and transient responses to a variety of environmental stimuli. Results demonstrated that AI-2 levels increased with the steady-state culture growth rate. In addition, AI-2 increased following pulsed addition of glucose, Fe(III), NaCl, and dithiothreitol and decreased following aerobiosis, amino acid starvation, and isopropyl-beta-D-thiogalactopyranoside-induced expression of human interleukin-2 (hIL-2). In general, the AI-2 responses to several perturbations were indicative of a shift in metabolic activity or state of the cells induced by the individual stress. Because of our interest in the expression of heterologous proteins in E. coli, the transcription of four quorum-regulated genes and 20 stress genes was mapped during the transient response to induced expression of hIL-2. Significant regulatory overlap was revealed among several stress and starvation genes and known quorum-sensing genes.

Aerobiosis↗
PubMed2004

Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces multiple virulence factors and causes different types of infections. Previous clinical studies identified P. aeruginosa isolates that lack individual virulence factors. However, the impact of losing several virulence factors simultaneously on the in vivo virulence of P. aeruginosa is not completely understood. The P. aeruginosa cell-to-cell communication system, or quorum sensing (QS), controls the production of several virulence factors. Animal studies using constructed QS mutants indicated that loss of the QS system severely impacts the virulence of P. aeruginosa. In this study, we tried to determine if deficiency within the QS system compromises the ability of P. aeruginosa to establish infections in humans. We have identified five QS-deficient strains through screening 200 isolates from patients with urinary tract, lower respiratory tract and wound infections. These strains lacked LasB and LasA activities and produced either no or very low levels of the autoinducers N-(3-oxododecanoyl) homoserine lactone and N-butyryl homoserine lactone. PCR analysis revealed that three isolates contained all four QS genes (lasI, lasR, rhlI and rhlR) while two isolates lacked both the lasR and rhlR genes. We also examined the five isolates for other virulence factors. The isolates produced variable levels of exotoxin A and, with one exception, were deficient in pyocyanin production. One isolate produced the type III secretion system (TTSS) effector proteins ExoS and ExoT, two isolates produced ExoT only and two isolates produced no TTSS proteins. The isolates produced weak to moderate biofilms on abiotic surfaces. Analysis of the patients' data revealed that two of the isolates represented a single strain that was isolated twice from the same patient within a 1 month interval. One QS-deficient clinical isolate (CI-1) lacked all tested virulence factors and produced a weak biofilm. These results suggest that naturally occurring QS-deficient strains of P. aeruginosa do occur and are capable of causing infections; and, that besides the known virulence factors, additional factors may contribute to the ability of certain strains such as CI-1 to establish an infection.

4-Butyrolactone↗
PubMed2004

Bacterial social engagements.

Quorum sensing is a process that enables bacteria to communicate using secreted signaling molecules called autoinducers. This process enables a population of bacteria to regulate gene expression collectively and, therefore, control behavior on a community-wide scale. Quorum sensing is widespread in the bacterial world and, generally, processes controlled by quorum sensing are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group. Cell-cell communication can occur within and between bacterial species, and between bacteria and their eukaryotic hosts, which suggests that the chemical lexicon is complex. Prokaryotic and eukaryotic mechanisms for enhancing and inhibiting quorum sensing have been identified, which suggests that manipulation of quorum-sensing-controlled processes could be common in bacterial-bacterial and bacterial-eukaryotic associations.

Bacteria↗
PubMed2001

A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism.

The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 infects both plants and animals. Previously, using plants to screen directly for P. aeruginosa virulence-attenuated mutants, we identified a locus, pho34B12, relevant in mammalian pathogenesis. Here, nonsense point mutations in the two opposing ORFs identified in the pho34B12 locus revealed that one of them, mvfR (multiple virulence factor Regulator), is able to control all of the phenotypes that mutant phoA34B12 displays. Both genetic and biochemical evidence demonstrate that the mvfR gene encodes a LysR-like transcriptional factor that positively regulates the production of elastase, phospholipase, and of the autoinducers, 3oxo-dodecanoyl homoserine lactone (PAI I) and 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as the expression of the phnAB operon, involved in phenazine biosynthesis. We demonstrate that the MvfR protein is membrane-associated and acts as a transcriptional activator until cells reach stationary phase, when a unique negative feedback mechanism is activated to signal the down-regulation of the MvfR protein. This work reveals an unprecedented virulence mechanism of P. aeruginosa and identifies a unique indispensable player in the P. aeruginosa quorum-sensing cascade.

Animals↗