Interspecies communication betweenBurkholderia cepaciaandPseudomonas aeruginosa

2002 ◽  
Vol 48 (8) ◽  
pp. 707-716 ◽  
Author(s):  
Shawn Lewenza ◽  
Michelle B Visser ◽  
Pamela A Sokol
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
Bacterial Population ◽  
Homoserine Lactone ◽  
Pulmonary Infections ◽  
Opportunistic Pathogens ◽  
Interspecies Communication ◽  
Sensing Systems

Burkholderia cepacia and Pseudomonas aeruginosa are opportunistic pathogens that commonly cause pulmonary infections in cystic fibrosis patients and occasionally co-infect patients' lungs. Both organisms possess quorum-sensing systems dependent on N-acyl homoserine lactone (N-acyl-HSL). Cross-feeding assays demonstrated that P. aeruginosa and B. cepacia were able to utilize heterologous N-acyl-HSL signaling molecules. The ability of quorum-sensing genes from one species to complement the respective quorum-sensing mutations in the heterologous species was also examined. These studies suggest that B. cepacia CepR can use N-acyl-HSLs synthesized by RhlI and LasI and that P. aeruginosa LasR and RhlR can use N-acyl-HSLs synthesized by CepI. It is possible that a mixed bacterial population of B. cepacia and P. aeruginosa can coordinately regulate some of their virulence factors and influence the progression of lung disease due to infection with these organisms.Key words: quorum sensing, Burkholderia cepacia, Pseudomonas aeruginosa, cystic fibrosis.

scholarly journals Inhibition of Quorum Sensing in Pseudomonas aeruginosa by N-Acyl Cyclopentylamides

2007 ◽  
Vol 73 (10) ◽  
pp. 3183-3188 ◽  
Author(s):  
Takenori Ishida ◽  
Tsukasa Ikeda ◽  
Noboru Takiguchi ◽  
Akio Kuroda ◽  
Hisao Ohtake ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Homoserine Lactone ◽  
Ring Structure ◽  
Response Regulators ◽  
Maximal Inhibition ◽  
Sensing Systems ◽  
Reporter Assays

ABSTRACT N-Octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhlA-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-Decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor, and its concentrations required for half-maximal inhibition for lasB-lacZ and rhlA-lacZ expression were 80 and 90 μM, respectively. C10-CPA also inhibited production of virulence factors, including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-l-homoserine lactone (PAI1) and rhlA-lacZ by N-butanoyl-l-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum-sensing systems via inhibiting interaction between their response regulators (LasR and RhlR) and autoinducers.

scholarly journals Functional Quorum Sensing Systems are Maintained during Chronic Burkholderia cepacia Complex Infections in Patients with Cystic Fibrosis

2011 ◽  
Vol 203 (3) ◽  
pp. 383-392 ◽  
Author(s):  
Suzanne A. McKeon ◽  
David T. Nguyen ◽  
Duber F. Viteri ◽  
James E. A. Zlosnik ◽  
Pamela A. Sokol
Keyword(s):  
Cystic Fibrosis ◽  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
Burkholderia Cepacia Complex ◽  
Sensing Systems

scholarly journals The Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-Oxododecanoyl)Homoserine Lactone Contributes to Virulence and Induces Inflammation In Vivo

2002 ◽  
Vol 184 (4) ◽  
pp. 1132-1139 ◽  
Author(s):  
Roger S. Smith ◽  
Sarah G. Harris ◽  
Richard Phipps ◽  
Barbara Iglewski
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
T Cell Activation ◽  
Cell Activation ◽  
White Blood Cells ◽  
Homoserine Lactone ◽  
Tissue Destruction ◽  
Sensing Systems ◽  
Cox 2

ABSTRACT Pseudomonas aeruginosa has two well-characterized quorum-sensing systems, Las and Rhl. These systems are composed of LuxR-type proteins, LasR and RhlR, and two acyl homoserine lactone (AHL) synthases, LasI and RhlI. LasI catalyzes the synthesis of N-(3-oxododecanoyl)homoserine lactone (3O-C12-HSL), whereas RhlI catalyzes the synthesis of N-butyryl-homoserine lactone. There is little known about the importance of AHLs in vivo and what effects these molecules have on eukaryotic cells. In order to understand the role of AHLs in vivo, we first tested the effects that deletions of the synthase genes in P. aeruginosa had on colonization of the lung. We demonstrate that in an adult mouse acute-pneumonia model, deletion of the lasI gene or both the lasI and rhlI genes greatly diminished the ability of P. aeruginosa to colonize the lung. To determine whether AHLs have a direct effect on the host, we examined the effects of 3O-C12-HSL injected into the skin of mice. In this model, 3O-C12-HSL stimulated a significant induction of mRNAs for the cytokines interleukin-1α (IL-1α) and IL-6 and the chemokines macrophage inflammatory protein 2 (MIP-2), monocyte chemotactic protein 1, MIP-1β, inducible protein 10, and T-cell activation gene 3. Additionally, dermal injections of 3O-C12-HSL also induced cyclooxygenase 2 (Cox-2) expression. The Cox-2 enzyme is important for the conversion of arachidonic acid to prostaglandins and is associated with edema, inflammatory infiltrate, fever, and pain. We also demonstrate that 3O-C12-HSL activates T cells to produce the inflammatory cytokine gamma interferon and therefore potentially promotes a Th1 environment. Induction of these inflammatory mediators in vivo is potentially responsible for the significant influx of white blood cells and subsequent tissue destruction associated with 3O-C12-HSL dermal injections. Therefore, the quorum-sensing systems of P. aeruginosa contribute to its pathogenesis both by regulating expression of virulence factors (exoenzymes and toxins) and by inducing inflammation.

scholarly journals Pseudomonas aeruginosa Quorum-Sensing Systems May Control Virulence Factor Expression in the Lungs of Patients with Cystic Fibrosis

2002 ◽  
Vol 70 (4) ◽  
pp. 1783-1790 ◽  
Author(s):  
David L. Erickson ◽  
Ryan Endersby ◽  
Amanda Kirkham ◽  
Kent Stuber ◽  
Dolina D. Vollman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Target Genes ◽  
Biologically Active ◽  
Virulence Determinants ◽  
Transcript Accumulation ◽  
Sensing Systems ◽  
Factor Expression

ABSTRACT Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically active levels of N-(3-oxododecanoyl)-l-homoserine (3-oxo-C12-HSL) and N-butyryl-l-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene lasI and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between the expression of lasI and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems are active and may control virulence factor expression in the lungs of patients with CF.

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 Instantaneous Within-Patient Diversity of Pseudomonas aeruginosa Quorum-Sensing Populations from Cystic Fibrosis Lung Infections

2009 ◽  
Vol 77 (12) ◽  
pp. 5631-5639 ◽  
Author(s):  
Cara N. Wilder ◽  
Gopal Allada ◽  
Martin Schuster
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Loss Of Function ◽  
Selective Forces ◽  
Lung Infections

ABSTRACT In the opportunistic pathogen Pseudomonas aeruginosa, acyl-homoserine lactone (acyl-HSL) quorum sensing (QS) regulates biofilm formation and expression of many extracellular virulence factors. Curiously, QS-deficient variants, often carrying mutations in the central QS regulator LasR, are frequently isolated from infections, particularly from cystic fibrosis (CF) lung infections. Very little is known about the proportion and diversity of these QS variants in individual infections. Such information is desirable to better understand the selective forces that drive the evolution of QS phenotypes, including social cheating and innate (nonsocial) benefits. To obtain insight into the instantaneous within-patient diversity of QS, we assayed a panel of 135 concurrent P. aeruginosa isolates from eight different adult CF patients (9 to 20 isolates per patient) for various QS-controlled phenotypes. Most patients contained complex mixtures of QS-proficient and -deficient isolates. Among all patients, deficiency in individual phenotypes ranged from 0 to about 90%. Acyl-HSL, sequencing, and complementation analyses of variants with global loss-of-function phenotypes revealed dependency upon the central QS circuitry genes lasR, lasI, and rhlI. Deficient and proficient isolates were clonally related, implying evolution from a common ancestor in vivo. Our results show that the diversity of QS types is high within and among patients, suggesting diverse selection pressures in the CF lung. A single selective mechanism, be it of a social or nonsocial nature, is unlikely to account for such heterogeneity. The observed diversity also shows that conclusions about the properties of P. aeruginosa QS populations in individual CF infections cannot be drawn from the characterization of one or a few selected isolates.

scholarly journals The Pseudomonas Quinolone Signal Regulates rhl Quorum Sensing in Pseudomonas aeruginosa

2000 ◽  
Vol 182 (10) ◽  
pp. 2702-2708 ◽  
Author(s):  
Susan L. McKnight ◽  
Barbara H. Iglewski ◽  
Everett C. Pesci
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Sensing System ◽  
Sensing Systems ◽  
Pseudomonas Quinolone Signal ◽  
Quorum Sensing System ◽  
Encoding Gene

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa uses intercellular signals to control the density-dependent expression of many virulence factors. The las and rhlquorum-sensing systems function, respectively, through the autoinducersN-(3-oxododecanoyl)-l-homoserine lactone andN-butyryl-l-homoserine lactone (C4-HSL), which are known to positively regulate the transcription of the elastase-encoding gene, lasB. Recently, we reported that a second type of intercellular signal is involved in lasB induction. This signal was identified as 2-heptyl-3-hydroxy-4-quinolone and designated thePseudomonas quinolone signal (PQS). PQS was determined to be part of the quorum-sensing hierarchy since its production and bioactivity depended on the las and rhlquorum-sensing systems, respectively. In order to define the role of PQS in the P. aeruginosa quorum-sensing cascade,lacZ gene fusions were used to determine the effect of PQS on the transcription of the quorum-sensing system geneslasR, lasI, rhlR, andrhlI. We found that in P. aeruginosa, PQS caused a major induction of rhlI′-lacZ and had lesser effects on the transcription of lasR′-lacZ andrhlR′-lacZ. We also observed that the transcription of bothrhlI′-lacZ and lasB′-lacZ was cooperatively effected by C4-HSL and PQS. Additionally, we present data indicating that PQS was not produced maximally until cultures reached the late stationary phase of growth. Taken together, our results imply that PQS acts as a link between the las and rhlquorum-sensing systems and that this signal is not involved in sensing cell density.

scholarly journals Genetic and transcriptomic characteristics of RhlR-dependent quorum sensing in cystic fibrosis isolates of Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Kyle L Asfahl ◽  
Nicole E Smalley ◽  
Alexandria P Chang ◽  
Ajai A Dandekar
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Signaling Mechanism ◽  
Genetic Characteristics ◽  
Genes Encoding ◽  
A Cell

In people with the genetic disease cystic fibrosis (CF), bacterial infections involving the opportunistic pathogen Pseudomonas aeruginosa are a significant cause of morbidity and mortality. P. aeruginosa uses a cell-cell signaling mechanism called quorum sensing (QS) to regulate many virulence functions. One type of QS consists of acyl-homoserine lactone (AHL) signals produced by LuxI-type signal synthases, which bind a cognate LuxR-type transcription factor. In laboratory strains and conditions, P. aeruginosa employs two AHL synthase/receptor pairs arranged in a hierarchy, with the LasI/R system controlling the RhlI/R system and many downstream virulence factors. However, P. aeruginosa isolates with inactivating mutations in lasR are frequently isolated from chronic CF infections. We and others have shown that these isolates frequently use RhlR as the primary QS regulator. RhlR is rarely mutated in CF and environmental settings. We were interested if there were reproducible genetic characteristics of these isolates and if there was a central group of genes regulated by RhlR in all isolates. We examined five isolates and found signatures of adaptation common to CF isolates. We did not identify a common genetic mechanism to explain the switch from Las- to Rhl-dominated QS. We describe a core RhlR regulon encompassing 20 genes encoding 7 products. These results suggest a key group of QS-regulated factors important for pathogenesis of chronic infection, and position RhlR as a target for anti-QS therapeutics. Our work underscores the need to sample a diversity of isolates to understanding QS beyond what has been described in laboratory strains.

scholarly journals Expression of the bviIR and cepIR Quorum-Sensing Systems of Burkholderia vietnamiensis

2007 ◽  
Vol 189 (8) ◽  
pp. 3006-3016 ◽  
Author(s):  
Rebecca J. Malott ◽  
Pamela A. Sokol
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
Regulatory Element ◽  
Transcriptional Regulator ◽  
Homoserine Lactone ◽  
Burkholderia Vietnamiensis ◽  
Sensing System ◽  
Sensing Systems ◽  
Quorum Sensing System ◽  
Regulatory Organization

ABSTRACT Burkholderia vietnamiensis has both the cepIR quorum-sensing system that is widely distributed among the Burkholderia cepacia complex (BCC) and the bviIR system. Comparison of the expression of cepI, cepR, bviI, and bviR-luxCDABE fusions in B. vietnamiensis G4 and the G4 cepR and bviR mutants determined that the expression of bviI requires both a functional cognate regulator, BviR, and functional CepR. The cepIR system, however, is not regulated by BviR. Unlike the cepIR genes in other BCC species, the cepIR genes are not autoregulated in G4. N-Acyl-homoserine lactone (AHL) production profiles in G4 cepI, cepR, bviI, and bviR mutants confirmed the regulatory organization of the G4 quorum-sensing systems. The regulatory network in strain PC259 is similar to that in G4, except that CepR positively regulates cepI and negatively regulates cepR. AHL production and the bviI expression levels in seven B. vietnamiensis isolates were compared. All strains produced N-octanoyl-homoserine lactone and N-hexanoyl-homoserine lactone; however, only one of four clinical strains but all three environmental strains produced the BviI synthase product, N-decanoyl-homoserine lactone (DHL). The three strains that did not produce DHL expressed bviR but not bviI. Heterologous expression of bviR restored DHL production in these strains. The bviIR loci of the non-DHL-producing strains were sequenced to confirm that bviR encodes a functional transcriptional regulator. Lack of expression of G4 bviI in these three strains indicated that an additional regulatory element may be involved in the regulation of bviIR expression in certain strains of B. vietnamiensis.

scholarly journals Social cheating in aPseudomonas aeruginosaquorum-sensing variant

2019 ◽  
Vol 116 (14) ◽  
pp. 7021-7026 ◽  
Author(s):  
Ruiyi Chen ◽  
Eric Déziel ◽  
Marie-Christine Groleau ◽  
Amy L. Schaefer ◽  
E. Peter Greenberg
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Genetic Disease ◽  
Social Evolution ◽  
Bacterial Pathogen ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Wild Type ◽  
Extracellular Metabolites

The opportunistic bacterial pathogenPseudomonas aeruginosahas a layered acyl-homoserine lactone (AHL) quorum-sensing (QS) system, which controls production of a variety of extracellular metabolites and enzymes. The LasRI system activates genes including those coding for the extracellular protease elastase and for the second AHL QS system, RhlRI. Growth ofP. aeruginosaon casein requires elastase production and LasR-mutant social cheats emerge in populations growing on casein.P. aeruginosacolonizes the lungs of individuals with the genetic disease cystic fibrosis (CF), and LasR mutants can be isolated from the colonized lungs; however, unlike laboratory-generated LasR mutants, many of these CF isolates have functioning RhlR-RhlI systems. We show that one such mutant can use the RhlR-RhlI system to activate expression of elastase and grow on casein. We carried out social-evolution experiments by growing this isolate on caseinate and, as with wild-typeP. aeruginosa, elastase-negative mutants emerge as cheats, but these are not RhlR mutants; rather, they are mutants that do not produce the non-AHLPseudomonasquinolone signal (PQS). Furthermore, we generated a RhlRI mutant and showed it had a fitness defect when growing together with the parent. Apparently, RhlR QS and PQS collude to support growth on caseinate in the absence of a functional LasR. Our findings provide a plausible explanation as to whyP. aeruginosaLasR mutants, but not RhlR mutants, are common in CF lungs.

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