Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa

Jensen, Peter Østrup; Bjarnsholt, Thomas; Phipps, Richard Kerry; Rasmussen, Trine Bernholdt; Calum, Henrik; Christoffersen, Lise-Lotte; Moser, Claus; Williams, Paul; Pressler, Tacjana; Givskov, Michael; Høiby, Niels

doi:10.1099/mic.0.2006/003863-0

Cited by 375 publications

(363 citation statements)

References 49 publications

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“…To date, it is commonly assumed that neutrophil death, possibly accelerated by resident bacteria, occurs rapidly upon recruitment to CF airways (6,7). Passive release of NE and other toxic by-products (myeloperoxidase, DNA, actin) is thought to ensue (8), perpetuating inflammation (3), infection, and obstruction (9).…”

mentioning

confidence: 99%

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways

Tirouvanziam

Gernez²,

Conrad³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

130

169

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Blood neutrophils recruited to cystic fibrosis (CF) airways are believed to be rapidly killed by resident bacteria and to passively release elastase and other toxic by-products that promote disease progression. By single-cell analysis, we demonstrate that profound functional and signaling changes readily occur within viable neutrophils recruited to CF airways, compared with their blood counterparts. Airway neutrophils have undergone conventional activation, as shown by decreased intracellular glutathione, increased lipid raft assembly, surface mobilization of CD11b؉ and CD66b؉ granules, and increased levels of the cytoskeleton-associated phospho-Syk kinase. Unexpectedly, they also mobilize to the surface CD63؉ elastase-rich granules, usually confined intracellularly, and lose surface expression of CD16 and CD14, both key receptors in phagocytosis. Furthermore, they express CD80, major histocompatibility complex type II, and the prostaglandin D2 receptor CD294, all normally associated with other lineages, which reflects functional reprogramming. This notion is reinforced by their decreased total phosphotyrosine levels, mirroring a postactivated stage, and increased levels of the phospho-S6 ribosomal protein, a key anabolic switch. Thus, we identified a subset of neutrophils within CF airways with a viable but dysfunctional phenotype. This subset provides a possible therapeutic target and indicates a need to revisit current paradigms of CF airway disease.cystic fibrosis transmembrane conductance regulator ͉ flow cytometry ͉ inflammation ͉ lung disease ͉ phosphoepitope

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mentioning

confidence: 99%

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways

Tirouvanziam

Gernez²,

Conrad³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

130

169

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“…One notable feature of biofilms is the protection that is offered to their component cells from antimicrobial agents and external forces including predation and the immune system (Costerton et al, 1987) Rhamnolipids do play a role in the chemical ecology of biofilms Rhamnolipid production within R aeruginosa biofilms has been shown to cause the rapid killing of polymorphonuclear leukocytes during experimental lung infections of mice (Jensen et al, 2007). From a microbial competition perspective, rhamnolipids, produced by R aeruginosa have been shown to be able to disrupt preformed biofilms of Bordetella bronchiseptica (Irie et al, 2005).…”

Section: Rhamnolipid Biosurfactantmentioning

confidence: 99%

Quorum sensing: implications on Rhamnolipid biosurfactant production

Dusane

Zinjarde

Venugopalan

et al. 2010

Biotechnology and Genetic Engineering Reviews

148

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Quorum sensing (QS) has received significant attention in the past few decades. QS describes population density dependent cell to cell communication in bacteria using diffusible signal molecules. These signal molecules produced by bacterial cells, regulate various physiological processes important for social behavior and pathogenesis. One such process regulated by quorum sensing molecules is the production of a biosurfactant, rhamnolipid. Rhamnolipids are important microbially derived surface active agents produced by Pseudomonas spp. under the control of two interrelated quorum sensing systems; namely las and rhl. Rhamnolipids possess antibacterial, antifungal and antiviral properties. They are important in motility, cell to cell interactions, cellular differentiation and formation of water channels that Biotechnology and Genetic Engineering Reviews -Vol. 27, 159-184 (2010) Quorum sensing (QS) has received significant attention in the past few decades. QS describes population density dependent cell to cell communication in bacteria using diffusible signal molecules. These signal molecules produced by bacterial cells, regulate various physiological processes important for social behavior and pathogenesis. One such process regulated by quorum sensing molecules is the production of a biosurfactant, rhamnolipid Rhamnolipids are important microbially derived surface active agents produced by Pseudomonas spp. under the control of two interrelated quorum sensing systems; namely las and rhl Rhamnolipids possess antibacterial, antifungal and antiviral properties. They are important in motility, cell to cell interactions, cellular differentiation and formation of water channels that *To whom correspondence may be addressed (p.rahman@tees.ac.uk) Abbreviations: QS: quorum sensing; AI: autoinducer; HSL: homoserine lactone; AHL: acyl homoserine lactone; PQS: pseudomonas quinolone signal; sRNA: small ribonucleic acid; RL: rhamnolipid; HAA: 3-(3-hydroxyalkanoyloxy) alkanoic acid; CTAB: cetyl trimethyl ammonium bromide; TLC: thin layer chromatography; GC: gas chromatography; MS: mass spectroscopy; FTIR: fourier transform infrared spectroscopy; ATR: attenuated total reflectance; NMR: nuclear magnetic resonance; SDS: sodium dodecyl sulfate; CMC: critical micelle concentration; LPS: lipopolysaccharide; TMV: tobacco mosaic virus; PAT: pseudomonas autoinducer; FAD: flavin adenine dinucleotide; NAD: nicotinamide adenine dinucleotide; TDP: thiamine di-phosphate; mN/m-milli-Newton per meter 160 D.H. Dusane et al. are characteristics of Pseudomonas biofilms. Rhamnolipids have biotechnological applications in the uptake of hydrophobic substrates, bioremediation of contaminated soils and polluted waters. Rhamnolipid biosurfactants are biodegradable as compared to chemical surfactants and hence are more preferred in environmental applications. In this review, we examine the biochemical and genetic mechanism of rhamnolipid production by P. aeruginosa and propose the application of QS signal molecules in enhancing the rhamnoli...

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“…In addition to directly causing tissue destruction, elastase also protects P. aeruginosa during infection by degrading immunoglobulins and complement proteins (Bainbridge & Fick, 1989;Cripps et al, 1995). Another class of QS-controlled product that affects the immune system is rhamnolipids, bioactive molecules with surfactant properties, synthesized by RhlAB, with the most abundant being L-rhamnosyl-3-hydroxydecanoyl-3-hydroxydecanoate (rhamnolipid 1) and 2-O-a-L-rhamnopyranosyl-a-L-rhamnopyranosyl-b-hydroxydecanoyl-b-hydroxydecanoic acid (rhamnolipid 2, also referred to as rhamnolipid B by Jensen et al, 2007;Lang & Wullbrandt, 1999;Maier & Soberon-Chavez, 2000). Although rhamnolipids were initially proposed to play a role in maintaining void spaces between microcolonies or for biofilm dispersal in vitro, we have subsequently shown that PMNs are unable to eradicate bacterial cells within P. aeruginosa biofilms in vitro .…”

Section: Qs-regulated Virulence Factors Involved In Lung Infectionsmentioning

confidence: 99%

Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis

et al. 2008

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Pseudomonas aeruginosa is a ubiquitous bacterium that causes opportunistic infections in a range of host tissues and organs. Infections by P. aeruginosa are difficult to treat and hence there is interest in the development of effective therapeutics. One of the key mechanisms that P. aeruginosa uses to control the expression of many virulence factors is the N-acylated homoserine lactone (AHL) regulatory system. Hence, there is considerable interest in targeting this regulatory pathway to develop novel therapeutics for infection control. P. aeruginosa is the principal cause of microbial keratitis and of infections in cystic fibrosis (CF) sufferers, and AHL-dependent cell-to-cell signalling has been shown to be important for both infection types. However, keratitis tends to be an acute infection whereas infection of CF patients develops into a chronic, lifelong infection. Thus, it is unclear whether AHL-regulated virulence plays the same role during these infections. This review presents a comparison of the role of AHL signalling in P. aeruginosamediated microbial keratitis and chronic lung infections of CF patients. IntroductionAll evidence to date indicates that we are losing the race to combat what have been for the last 40 years simple bacterial infections. This is primarily due to the emergence of, and strong selection for, antibiotic-resistant bacteria, which has led to the current situation where many bacteria are so antibiotic resistant that patients can only be treated with what are considered to be drugs of last defence. A contributing factor in this steady failure of current drugs has been the strategy of making simple modifications of existing classes of antimicrobials to maintain a drug's activity over the short term. This process is no longer working, and what needs to be done is to identify and develop new drug targets. This will take significant effort and may require a paradigm shift in thinking about how we deal with pathogenic bacteria, and the development of therapeutics that are highly specific for bacterial groups or even individual organisms. However, such outcomes should not be seen as limitations, but as benefits, reducing the likelihood of general resistance developing. Furthermore, bacterial control does not necessarily require bactericidal activity; it may be sufficient to target genetic pathways that are essential for virulence or the infection process, but that are otherwise non-essential systems. One such system is the acylated homoserine lactone (AHL) quorum sensing (QS) system found in a range of pathogenic Gram-negative bacteria, e.g. Pseudomonas aeruginosa, Burkholderia cepacia and Serratia marcescens. P. aeruginosa is of particular interest because it forms biofilms that contribute to the infection process and many of its virulence factors, including biofilm development, are QS regulated. Furthermore, it causes infections in wounds, eyes and lungs (both chronic and acute). In fact, P. aeruginosa infection is the most frequent cause of mortality in cystic fibrosis sufferers and is...

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Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa

Cited by 375 publications

References 49 publications

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways

Quorum sensing: implications on Rhamnolipid biosurfactant production

Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis

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