scholarly journals Structural determinants driving homoserine lactone ligand selection in thePseudomonas aeruginosaLasR quorum-sensing receptor

2018 ◽  
Vol 116 (1) ◽  
pp. 245-254 ◽  
Author(s):  
Amelia R. McCready ◽  
Jon E. Paczkowski ◽  
Brad R. Henke ◽  
Bonnie L. Bassler
Keyword(s):  
Quorum Sensing ◽  
Ligand Binding ◽  
Homoserine Lactone ◽  
Communication Process ◽  
Signal Molecules ◽  
Structural Determinants ◽  
Homoserine Lactones ◽  
Ligand Selectivity ◽  
Ligand Promiscuity

Quorum sensing is a cell–cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use thePseudomonas aeruginosaLasR quorum-sensing receptor to explore signal discrimination. The cognate autoinducer, 3OC12homoserine lactone (3OC12HSL), is a more potent activator of LasR than other homoserine lactones. However, other homoserine lactones can elicit LasR-dependent quorum-sensing responses, showing that LasR displays ligand promiscuity. We identify mutants that alter which homoserine lactones LasR detects. Substitution at residue S129 decreases the LasR response to 3OC12HSL, while enhancing discrimination against noncognate autoinducers. Conversely, the LasR L130F mutation increases the potency of 3OC12HSL and other homoserine lactones. We solve crystal structures of LasR ligand-binding domains complexed with noncognate autoinducers. Comparison with existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop near the ligand-binding site. We show that LasR variants with modified ligand preferences exhibit altered quorum-sensing responses to autoinducers in vivo. We suggest that possessing some ligand promiscuity endows LasR with the ability to optimally regulate quorum-sensing traits.

scholarly journals ThePseudomonas aeruginosaLasR quorum-sensing receptor balances ligand selectivity and sensitivity

2018 ◽  
Author(s):  
Amelia R. McCready ◽  
Jon E. Paczkowski ◽  
Brad R. Henke ◽  
Bonnie L. Bassler
Keyword(s):  
Quorum Sensing ◽  
Ligand Binding ◽  
Cell Communication ◽  
Communication Process ◽  
Signal Molecules ◽  
Ligand Selectivity ◽  
Existing Structures ◽  
Binding Domains ◽  
Extracellular Signal ◽  
Sensitivity And Selectivity

AbstractQuorum sensing is a cell-cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by extracellular signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use thePseudomonas aeruginosaLasR quorum-sensing receptor to explore receptor sensitivity and selectivity. Alteration of LasR amino acid S129 increases ligand selectivity and decreases ligand sensitivity. Conversely, the L130F mutation enhances LasR sensitivity while reducing selectivity. We solve crystal structures of LasR ligand binding domains complexed with non-cognate autoinducers. Comparison to existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop adjacent to the ligand binding site. We show thatP. aeruginosaharboring LasR variants with modified selectivity or sensitivity exhibit altered quorum-sensing responses. We suggest that an evolutionary trade-off between ligand selectivity and sensitivity enables LasR to optimally regulate quorum-sensing traits.

scholarly journals Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Rita S. Valente ◽  
Pol Nadal-Jimenez ◽  
André F. P. Carvalho ◽  
Filipe J. D. Vieira ◽  
Karina B. Xavier
Keyword(s):  
Signal Transduction ◽  
Quorum Sensing ◽  
Plant Pathogen ◽  
Bacterial Species ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Interspecies Interactions ◽  
Major Factors

ABSTRACT Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora), two signaling networks—the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway—control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae. This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae. This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways.

scholarly journals Biofilms on Indwelling Urethral Catheters Produce Quorum-Sensing Signal Molecules In Situ and In Vitro

1998 ◽  
Vol 64 (9) ◽  
pp. 3486-3490 ◽  
Author(s):  
David J. Stickler ◽  
Nicola S. Morris ◽  
Robert J. C. McLean ◽  
Clay Fuqua
Keyword(s):  
Quorum Sensing ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Feeding Assay ◽  
Gram Negative ◽  
Homoserine Lactones ◽  
Acylated Homoserine Lactones

ABSTRACT Acylated homoserine lactones (AHLs) are chemical signals that mediate population density-dependent (quorum-sensing) gene expression in numerous gram-negative bacteria. In this study, gram-negative bacilli isolated from catheters were screened for AHL production by a cross-feeding assay utilizing an AHL-responsive Agrobacterium tumefaciens reporter strain. Positive reactions were obtained from 14 isolates of Pseudomonas aeruginosa; negative or weakly positive reactions were recorded for isolates of five other species. P. aeruginosa biofilms were then produced on catheters in a physical model of the bladder. Sections of colonized all-silicone catheters gave positive reactions for the quorum-sensing signal molecules as did sections that had been cleaned of biofilm and autoclaved. Control sections of unused catheters were negative in the tests. Sections from four of nine catheters that had been freshly removed from patients gave positive reactions for AHLs. Cleaned autoclaved sections of three of these catheters also gave strongly positive reactions for AHLs. These results demonstrate that AHLs are produced by biofilms as they develop on the catheters both in vitro in the model and in vivo in the patient’s bladder. They represent the first demonstration of AHL production by biofilms in a clinical setting.

N-Acylhomoserine lactone quorum-sensing signalling in antagonistic phenazine-producing Pseudomonas isolates from the red cocoyam rhizosphere

Microbiology ◽  
2011 ◽  
Vol 157 (2) ◽  
pp. 459-472 ◽  
Author(s):  
K. De Maeyer ◽  
J. D'aes ◽  
G. K. H. Hua ◽  
M. Perneel ◽  
L. Vanhaecke ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Regulatory System ◽  
Homoserine Lactone ◽  
Antagonistic Activity ◽  
Signal Molecules ◽  
Pseudomonas Chlororaphis ◽  
Homoserine Lactones ◽  
Acylhomoserine Lactone ◽  
Phenazine Production ◽  
Phenazine Antibiotics

Forty fluorescent Pseudomonas strains isolated from white and red cocoyam roots were tested for their ability to synthesize N-acyl-l-homoserine lactones (acyl-HSLs). Remarkably, only isolates from the red cocoyam rhizosphere that were antagonistic against the cocoyam root rot pathogen Pythium myriotylum and synthesized phenazine antibiotics produced acyl-HSLs. This supports the assumption that acyl-HSL production is related to the antagonistic activity of the strains. After detection, the signal molecules were identified through TLC-overlay and liquid chromatography-multiple MS (LC-MS/MS) analysis. In our representative strain, Pseudomonas CMR12a, production of the signal molecules could be assigned to two quorum-sensing (QS) systems. The first one is the QS system for phenazine production, PhzI/PhzR, which seemed to be well conserved, since it was genetically organized in the same way as in the well-described phenazine-producing Pseudomonas strains Pseudomonas fluorescens 2-79, Pseudomonas chlororaphis PCL1391 and Pseudomonas aureofaciens 30-84. The newly characterized genes cmrI and cmrR make up the second QS system of CMR12a, under the control of the uncommon N-3-hydroxy-dodecanoyl-homoserine lactone (3-OH-C12-HSL) and with low similarity to other Pseudomonas QS systems. No clear function could yet be assigned to the CmrI/CmrR system, although it contributes to the biocontrol capability of CMR12a. Both the PhzI/PhzR and CmrI/CmrR systems are controlled by the GacS/GacA two-component regulatory system.

scholarly journals A Marine Mesorhizobium sp. Produces Structurally Novel Long-Chain N-Acyl-l-Homoserine Lactones

2007 ◽  
Vol 73 (11) ◽  
pp. 3587-3594 ◽  
Author(s):  
Anja Krick ◽  
Stefan Kehraus ◽  
Leo Eberl ◽  
Kathrin Riedel ◽  
Heidrun Anke ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Solid Phase ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Cytotoxic Activities ◽  
Rrna Gene ◽  
Liquid Chromatography Mass Spectrometry ◽  
Homoserine Lactones ◽  
Chain Lengths ◽  
Acylated Homoserine Lactones

ABSTRACT Our study focused on a Mesorhizobium sp. that is phylogenetically affiliated by 16S rRNA gene sequence to other marine and saline bacteria of this genus. Liquid chromatography-mass spectrometry investigations of the extract obtained from solid-phase extraction of cultures of this bacterium indicated the presence of several N-acyl homoserine lactones (AHLs), with chain lengths of C10 to C16. Chromatographic separation of the active bacterial extract yielded extraordinarily large amounts of two unprecedented acylated homoserine lactones, 5-cis-3-oxo-C12-homoserine lactone (5-cis-3-oxo-C12-HSL) (compound 1) and 5-cis-C12-HSL (compound 2). Quorum-sensing activity of compounds 1 and 2 was shown in two different biosensor systems [Escherichia coli MT102(pSB403) and Pseudomonas putida F117(pKR-C12)]. Furthermore, it was shown that both compounds can restore protease and pyoverdin production of an AHL-deficient Pseudomonas aeruginosa PAO1 lasI rhlI double mutant, suggesting that these signal molecules maybe used for intergenus signaling. In conclusion, these data indicate that the quorum-sensing activity of compounds 1 and 2 is modulated by the chain length and functional groups of the acyl moiety. Additionally, compound 1 showed antibacterial and cytotoxic activities.

scholarly journals N-3-Hydroxy Dodecanoyl-DL-homoserine Lactone (OH-dDHL) Triggers Apoptosis of Bone Marrow-Derived Macrophages through the ER- and Mitochondria-Mediated Pathways

2021 ◽  
Vol 22 (14) ◽  
pp. 7565
Author(s):  
Kyungho Woo ◽  
Dong Ho Kim ◽  
Man Hwan Oh ◽  
Ho Sung Park ◽  
Chul Hee Choi
Keyword(s):  
Bone Marrow ◽  
Quorum Sensing ◽  
Deletion Mutant ◽  
Transmembrane Protein ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Host Responses ◽  
Wild Type ◽  
Mutant Strains

Quorum sensing of Acinetobacter nosocomialis for cell-to-cell communication produces N-3-hydroxy dodecanoyl-DL-homoserine lactone (OH-dDHL) by an AnoR/I two-component system. However, OH-dDHL-driven apoptotic mechanisms in hosts have not been clearly defined. Here, we investigated the induction of apoptosis signaling pathways in bone marrow-derived macrophages treated with synthetic OH-dDHL. Moreover, the quorum-sensing system for virulence regulation was evaluated in vivo using wild-type and anoI-deletion mutant strains. OH-dDHL decreased the viability of macrophage and epithelial cells in dose- and time-dependent manners. OH-dDHL induced Ca2+ efflux and caspase-12 activation by ER stress transmembrane protein (IRE1 and ATF6a p50) aggregation and induced mitochondrial dysfunction through reactive oxygen species (ROS) production, which caused cytochrome c to leak. Pretreatment with a pan-caspase inhibitor reduced caspase-3, -8, and -9, which were activated by OH-dDHL. Pro-inflammatory cytokine and paraoxonase-2 (PON2) gene expression were increased by OH-dDHL. We showed that the anoI-deletion mutant strains have less intracellular invasion compared to the wild-type strain, and their virulence, such as colonization and dissemination, was decreased in vivo. Consequently, these findings revealed that OH-dDHL, as a virulence factor, contributes to bacterial infection and survival as well as the modification of host responses in the early stages of infection.

scholarly journals Quorum Sensing: a Transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

2004 ◽  
Vol 72 (11) ◽  
pp. 6589-6596 ◽  
Author(s):  
Ricky L. Ulrich ◽  
David DeShazer ◽  
Harry B. Hines ◽  
Jeffrey A. Jeddeloh
Keyword(s):  
Quorum Sensing ◽  
Virulence Factor ◽  
Regulatory System ◽  
In Silico Analysis ◽  
Homoserine Lactone ◽  
Burkholderia Mallei ◽  
Wild Type ◽  
Transcriptional Regulatory ◽  
A Cell

ABSTRACT Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanism termed quorum sensing (QS). An in silico analysis of the Burkholderia mallei ATCC 23344 genome revealed that it encodes at least two luxI and four luxR homologues. Using mass spectrometry, we showed that wild-type B. mallei produces the signaling molecules N-octanoyl-homoserine lactone and N-decanoyl-homoserine lactone. To determine if QS is involved in the virulence of B. mallei, we generated mutations in each putative luxIR homologue and tested the pathogenicities of the derivative strains in aerosol BALB/c mouse and intraperitoneal hamster models. Disruption of the B. mallei QS alleles, especially in RJ16 (bmaII) and RJ17 (bmaI3), which are luxI mutants, significantly reduced virulence, as indicated by the survival of mice who were aerosolized with 104 CFU (10 50% lethal doses [LD50s]). For the B. mallei transcriptional regulator mutants (luxR homologues), mutation of the bmaR5 allele resulted in the most pronounced decrease in virulence, with 100% of the challenged animals surviving a dose of 10 LD50s. Using a Syrian hamster intraperitoneal model of infection, we determined the LD50s for wild-type B. mallei and each QS mutant. An increase in the relative LD50 was found for RJ16 (bmaI1) (>967 CFU), RJ17 (bmaI3) (115 CFU), and RJ20 (bmaR5) (151 CFU) compared to wild-type B. mallei (<13 CFU). These findings demonstrate that B. mallei carries multiple luxIR homologues that either directly or indirectly regulate the biosynthesis of an essential virulence factor(s) that contributes to the pathogenicity of B. mallei in vivo.

Occurrence of Proteolytic Activity and N-Acyl-Homoserine Lactone Signals in the Spoilage of Aerobically Chill-Stored Proteinaceous Raw Foods

2006 ◽  
Vol 69 (11) ◽  
pp. 2729-2737 ◽  
Author(s):  
M. LIU ◽  
J. M. GRAY ◽  
M. W. GRIFFITHS
Keyword(s):  
Quorum Sensing ◽  
Proteolytic Activity ◽  
Food Systems ◽  
Bacterial Flora ◽  
Homoserine Lactone ◽  
Food Samples ◽  
Clear Correlation ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Raw Foods

Proteolytic pseudomonads dominate the spoilage flora of aerobically chill-stored proteinaceous raw foods. Proteolysis during spoilage of these food systems affects both food quality and the dynamics of the bacterial community because it increases the availability of nutrients to the community as a whole. Quorum sensing, or cell-cell signaling, is associated closely with ecological interactions among bacteria in mixed communities. The potential role of quorum sensing in proteolytic food spoilage was examined, based on the evaluation of N-acyl-homoserine lactone (AHL) signal molecules. The occurrence of proteolytic activity and AHL signals was studied during spoilage of aerobically chill-stored ground beef, fish, chicken, and raw milk. Pseudomonads dominated the psychrotrophic flora, followed distantly by members of the Enterobacteriaceae. The growth of pseudomonads was correlated with the occurrence of proteolytic activity in all food systems. AHL concentration began increasing significantly only after the onset of proteolytic activity. Widely divergent AHL profiles were revealed by thin-layer chromatography analysis of the different food samples, and these profiles were likely determined by the undefined bacterial flora in these systems and by the characterized pseudomonads and Enterobacteriaceae. Although Hafnia alvei was a major component of the Enterobacteriaceae flora in all foods tested and a strong AHL producer, the signal molecules produced by H. alvei strain EB1 did not influence protease production by Pseudomonas fluorescens strain 395 in vitro. These results do not indicate any clear correlation between the overall detectable AHL signal molecules accumulated in the food samples and proteolytic activity.

Novel bacteria degrading N-acylhomoserine lactones and their use as quenchers of quorum-sensing-regulated functions of plant-pathogenic bacteria

Microbiology ◽  
2003 ◽  
Vol 149 (8) ◽  
pp. 1981-1989 ◽  
Author(s):  
Stéphane Uroz ◽  
Cathy D'Angelo-Picard ◽  
Aurélien Carlier ◽  
Miena Elasri ◽  
Carine Sicot ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Pathogenic Bacteria ◽  
Rhodococcus Erythropolis ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
In Planta ◽  
Signal Molecule ◽  
Violacein Production ◽  
Regulated Functions

Bacteria degrading the quorum-sensing (QS) signal molecule N-hexanoylhomoserine lactone were isolated from a tobacco rhizosphere. Twenty-five isolates degrading this homoserine lactone fell into six groups according to their genomic REP-PCR and rrs PCR-RFLP profiles. Representative strains from each group were identified as members of the genera Pseudomonas, Comamonas, Variovorax and Rhodococcus. All these isolates degraded N-acylhomoserine lactones other than the hexanoic acid derivative, albeit with different specificity and kinetics. One of these isolates, Rhodococcus erythropolis strain W2, was used to quench QS-regulated functions of other microbes. In vitro, W2 strongly interfered with violacein production by Chromobacterium violaceum, and transfer of pathogenicity in Agrobacterium tumefaciens. In planta, R. erythropolis W2 markedly reduced the pathogenicity of Pectobacterium carotovorum subsp. carotovorum in potato tubers. These series of results reveal the diversity of the QS-interfering bacteria in the rhizosphere and demonstrate the validity of targeting QS signal molecules to control pathogens with natural bacterial isolates.

scholarly journals Distribution of Quorum-Sensing Genes in the Burkholderia cepacia Complex

2001 ◽  
Vol 69 (7) ◽  
pp. 4661-4666 ◽  
Author(s):  
E. Lutter ◽  
S. Lewenza ◽  
J. J. Dennis ◽  
M. B. Visser ◽  
P. A. Sokol
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
Homoserine Lactone ◽  
Burkholderia Cepacia Complex ◽  
Homoserine Lactones

ABSTRACT The distribution of quorum-sensing genes among strains from seven genomovars of the Burkholderia cepaciacomplex was examined by PCR. cepR and cepI were amplified from B. cepacia genomovars I and III, B. stabilis, and B. vietnamiensis. cepR was also amplified from B. multivorans and B. cepacia genomovar VI. bviIR were amplified from B. vietnamiensis. All genomovars producedN-octanoyl-l-homoserine lactone andN-hexanoyl-l-homoserine lactone.B. vietnamiensis and B. cepacia genomovar VII produced additional N-acyl-l-homoserine lactones.

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