Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells

2009 ◽  
Vol 198 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Hongtao Li ◽  
Lili Wang ◽  
Lu Ye ◽  
Yan Mao ◽  
Xuhua Xie ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mast Cells ◽  
Quorum Sensing ◽  
Homoserine Lactone ◽  
Signal Molecule

scholarly journals Azithromycin Inhibits MUC5AC Production Induced by the Pseudomonas aeruginosa Autoinducer N-(3-Oxododecanoyl) Homoserine Lactone in NCI-H292 Cells

2004 ◽  
Vol 48 (9) ◽  
pp. 3457-3461 ◽  
Author(s):  
Yoshifumi Imamura ◽  
Katsunori Yanagihara ◽  
Yohei Mizuta ◽  
Masafumi Seki ◽  
Hideaki Ohno ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Bacterial Infection ◽  
Core Protein ◽  
Homoserine Lactone ◽  
Signal Molecule ◽  
Diffuse Panbronchiolitis ◽  
Mucin Production ◽  
Protein Levels ◽  
Extracellular Signal

ABSTRACT The features of chronic airway diseases, including chronic bronchitis, cystic fibrosis, bronchiectasis, and diffuse panbronchiolitis, include chronic bacterial infection and airway obstruction by mucus. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection, and quorum-sensing systems contribute to the pathogenesis of this disease. The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL)] not only regulates bacterial virulence but also is associated with the immune response. In this study, we investigated whether 3O-C12-HSL could stimulate the production of a major mucin core protein, MUC5AC. The effect of a macrolide on MUC5AC production was also studied. 3O-C12-HSL induced NCI-H292 cells to express MUC5AC at both the mRNA and the protein levels in time- and dose-dependent manners. A 15-membered macrolide, azithromycin, inhibited MUC5AC production that was activated by 3O-C12-HSL. 3O-C12-HSL induced extracellular signal-regulated kinase (ERK) 1/2 and I-κB phosphorylation in cells, and this induction was suppressed by azithromycin. 3O-C12-HSL-induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. Our findings suggest that the P. aeruginosa autoinducer 3O-C12-HSL contributes to excessive mucin production in chronic bacterial infection. Azithromycin seems to reduce this mucin production by interfering with intracellular signal transduction.

scholarly journals In vitro biosynthesis of the Pseudomonas aeruginosa quorum-sensing signal molecule N-butanoyl-L-homoserine lactone

2002 ◽  
Vol 28 (1) ◽  
pp. 193-203 ◽  
Author(s):  
Yan Jiang ◽  
Miguel Camara ◽  
Siri Ram Chhabra ◽  
Kim R. Hardie ◽  
Barrie W. Bycroft ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Homoserine Lactone ◽  
Signal Molecule ◽  
In Vitro Biosynthesis

scholarly journals A Distinct QscR Regulon in the Pseudomonas aeruginosa Quorum-Sensing Circuit

2006 ◽  
Vol 188 (9) ◽  
pp. 3365-3370 ◽  
Author(s):  
Yannick Lequette ◽  
Joon-Hee Lee ◽  
Fouzia Ledgham ◽  
Andrée Lazdunski ◽  
E. Peter Greenberg
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Signal Molecule ◽  
Control Of Gene Expression ◽  
Signaling Systems ◽  
Sensing Systems

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa possesses two complete acyl-homoserine lactone (acyl-HSL) signaling systems. One system consists of LasI and LasR, which generate a 3-oxododecanoyl-homoserine lactone signal and respond to that signal, respectively. The other system is RhlI and RhlR, which generate butanoyl-homoserine lactone and respond to butanoyl-homoserine lactone, respectively. These quorum-sensing systems control hundreds of genes. There is also an orphan LasR-RhlR homolog, QscR, for which there is no cognate acyl-HSL synthetic enzyme. We previously reported that a qscR mutant is hypervirulent and showed that QscR transiently represses a few quorum-sensing-controlled genes. To better understand the role of QscR in P. aeruginosa gene regulation and to better understand the relationship between QscR, LasR, and RhlR control of gene expression, we used transcription profiling to identify a QscR-dependent regulon. Our analysis revealed that QscR activates some genes and represses others. Some of the repressed genes are not regulated by the LasR-I or RhlR-I systems, while others are. The LasI-generated 3-oxododecanoyl-homoserine lactone serves as a signal molecule for QscR. Thus, QscR appears to be an integral component of the P. aeruginosa quorum-sensing circuitry. QscR uses the LasI-generated acyl-homoserine lactone signal and controls a specific regulon that overlaps with the already overlapping LasR- and RhlR-dependent regulons.

scholarly journals Quorum Quenching by an N-Acyl-Homoserine Lactone Acylase from Pseudomonas aeruginosa PAO1

2006 ◽  
Vol 74 (3) ◽  
pp. 1673-1682 ◽  
Author(s):  
Charles F. Sio ◽  
Linda G. Otten ◽  
Robbert H. Cool ◽  
Stephen P. Diggle ◽  
Peter G. Braun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Side Chain ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Beta Lactam ◽  
Signal Molecule ◽  
Pathogenic Potential

ABSTRACT The virulence of the opportunistic human pathogen Pseudomonas aeruginosa PAO1 is controlled by an N-acyl-homoserine lactone (AHL)-dependent quorum-sensing system. During functional analysis of putative acylase genes in the P. aeruginosa PAO1 genome, the PA2385 gene was found to encode an acylase that removes the fatty acid side chain from the homoserine lactone (HSL) nucleus of AHL-dependent quorum-sensing signal molecules. Analysis showed that the posttranslational processing of the acylase and the hydrolysis reaction type are similar to those of the beta-lactam acylases, strongly suggesting that the PA2385 protein is a member of the N-terminal nucleophile hydrolase superfamily. In a bioassay, the purified acylase was shown to degrade AHLs with side chains ranging in length from 11 to 14 carbons at physiologically relevant low concentrations. The substituent at the 3′ position of the side chain did not affect activity, indicating broad-range AHL quorum-quenching activity. Of the two main AHL signal molecules of P. aeruginosa PAO1, N-butanoyl-l-homoserine lactone (C4-HSL) and N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL), only 3-oxo-C12-HSL is degraded by the enzyme. Addition of the purified protein to P. aeruginosa PAO1 cultures completely inhibited accumulation of 3-oxo-C12-HSL and production of the signal molecule 2-heptyl-3-hydroxy-4(1H)-quinolone and reduced production of the virulence factors elastase and pyocyanin. Similar results were obtained when the PA2385 gene was overexpressed in P. aeruginosa. These results demonstrate that the protein has in situ quorum-quenching activity. The quorum-quenching AHL acylase may enable P. aeruginosa PAO1 to modulate its own quorum-sensing-dependent pathogenic potential and, moreover, offers possibilities for novel antipseudomonal therapies.

scholarly journals Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection

2012 ◽  
Vol 57 (1) ◽  
pp. 569-578 ◽  
Author(s):  
Moayad Alhariri ◽  
Abdelwahab Omri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Homoserine Lactone ◽  
Protease Production ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Signal Molecule ◽  
Intratracheal Administration ◽  
Content Type

ABSTRACTWe sought to investigate alterations in quorum-sensing signal moleculeN-acyl homoserine lactone secretion and in the release ofPseudomonas aeruginosavirulence factors, as well as thein vivoantimicrobial activity of bismuth-ethanedithiol incorporated into a liposome-loaded tobramycin formulation (LipoBiEDT-TOB) administered to rats chronically infected withP. aeruginosa. The quorum-sensing signal moleculeN-acyl homoserine lactone was monitored by using a biosensor organism.P. aeruginosavirulence factors were assessed spectrophotometrically. An agar beads model of chronicPseudomonaslung infection in rats was used to evaluate the efficacy of the liposomal formulation in the reduction of bacterial count. The levels of active tobramycin in the lungs and the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective in disrupting both quorum-sensing signal moleculesN-3-oxo-dodeccanoylhomoserine lactone andN-butanoylhomoserine lactone, as well as significantly (P< 0.05) reducing lipase, chitinase, and protease production. At 24 h after 3 treatments, the CFU counts in lungs of animals treated with LipoBiEDT-TOB were of 3 log10CFU/lung, comparated to 7.4 and 4.7 log10CFU/lung, respectively, in untreated lungs and in lungs treated with free antibiotic. The antibiotic concentration after the last dose of LipoBiEDT-TOB was 25.1 μg/lung, while no tobramycin was detected in the kidneys. As for the free antibiotic, we found 6.5 μg/kidney but could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB reduced the production of quorum-sensing molecules and virulence factors and could highly improve the management of chronic pulmonary infection in cystic fibrosis patients.

scholarly journals Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 712-723 ◽  
Author(s):  
Valérie Dekimpe ◽  
Eric Déziel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Transcriptional Regulator ◽  
Homoserine Lactone ◽  
The Other ◽  
Virulence Determinants ◽  
Late Stationary Phase ◽  
Regulatory Systems ◽  
Specific Factors

Pseudomonas aeruginosa uses the two major quorum-sensing (QS) regulatory systems las and rhl to modulate the expression of many of its virulence factors. The las system is considered to stand at the top of the QS hierarchy. However, some virulence factors such as pyocyanin have been reported to still be produced in lasR mutants under certain conditions. Interestingly, such mutants arise spontaneously under various conditions, including in the airways of cystic fibrosis patients. Using transcriptional lacZ reporters, LC/MS quantification and phenotypic assays, we have investigated the regulation of QS-controlled factors by the las system. Our results show that activity of the rhl system is only delayed in a lasR mutant, thus allowing the expression of multiple virulence determinants such as pyocyanin, rhamnolipids and C4-homoserine lactone (HSL) during the late stationary phase. Moreover, at this stage, RhlR is able to overcome the absence of the las system by activating specific LasR-controlled functions, including production of 3-oxo-C12-HSL and Pseudomonas quinolone signal (PQS). P. aeruginosa is thus able to circumvent the deficiency of one of its QS systems by allowing the other to take over. This work demonstrates that the QS hierarchy is more complex than the model simply presenting the las system above the rhl system.

scholarly journals Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosa

2008 ◽  
Vol 52 (10) ◽  
pp. 3648-3663 ◽  
Author(s):  
Mette E. Skindersoe ◽  
Morten Alhede ◽  
Richard Phipps ◽  
Liang Yang ◽  
Peter O. Jensen ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Dna Microarrays ◽  
Underlying Mechanism ◽  
Homoserine Lactone ◽  
Reverse Transcription Pcr ◽  
Animal Infection ◽  
Beneficial Action ◽  
Severe Infections

ABSTRACT During infection, Pseudomonas aeruginosa employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of P. aeruginosa, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with P. aeruginosa with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of P. aeruginosa. This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in P. aeruginosa. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of N-3-oxo-dodecanoyl-l-homoserine lactone.

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