Dubern JF, Diggle SP.. Quorum sensing by 2-alkyl-4-quinolones in Pseudomonas aeruginosa and other bacterial species. Mol Biosyst 4: 882-888

Institute of Infection, Immunity & Inflammation, Centre of Biomolecular Sciences, University of Nottingham, Nottingham, United Kingdom.
Molecular BioSystems (Impact Factor: 3.18). 10/2008; 4(9):882-8. DOI: 10.1039/b803796p
Source: PubMed

ABSTRACT Pseudomonas aeruginosa produces the cell-to-cell signal molecule 2-heptyl-3-hydroxy-4-quinolone (The Pseudomonas quinolone signal; PQS), which is integrated within a complicated quorum sensing signaling system. PQS belongs to the family of 2-alkyl-4-quinolones (AQs), which have been previously described for their antimicrobial activities. PQS is synthesized via the pqsABCDE operon which is responsible for generating multiple AQs including 2-heptyl-4-quinolone (HHQ), the immediate PQS precursor. In addition, PQS signaling plays an important role in P. aeruginosa pathogenesis because it regulates the production of diverse virulence factors including elastase, pyocyanin and LecA lectin in addition to affecting biofilm formation. Here, we summarize the most recent findings on the biosynthesis and regulation of PQS and other AQs including the discovery of AQs in other bacterial species.

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    • "The ability to cause such a wide array of infections is dependent on the expression of virulence factors (Strateva and Mitov 2011). Virulence factor regulation in P. aeruginosa is achieved through a density-dependent cell-to-cell communication network, involving three main quorum-sensing systems; the las, rhl (Schuster et al. 2013; Smith and Iglewski 2003) and Pseudomonas quinolone signal system (Dubern and Diggle 2008; Pesci et al. 1999). The las and rhl systems are LuxRI homologues, where lasI and rhlI direct synthesis of N-3- oxododecanoylhomoserine lactone (3-oxo-C12-HSL) and Nbutanoylhomoserine lactone (C4-HSL), respectively; these are diffusible signalling molecules which activate their respective DNA binding response regulators, LasR and RhlR, which, in turn, induces the expression of a wide range of genes, approximately 6 % of the genome (Schuster and Greenberg 2006; Schuster et al. 2013; Wagner et al. 2004; Williams et al. 2007). "
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    ABSTRACT: Rhamnolipids (RLs) are heterogeneous glycolipid molecules that are composed of one or two L-rhamnose sugars and one or two β-hydroxy fatty acids, which can vary in their length and branch size. They are biosurfactants, predominantly produced by Pseudomonas aeruginosa and are important virulence factors, playing a major role in P. aeruginosa pathogenesis. Therefore, a fast, accurate and high-throughput method of detecting such molecules is of real importance. Here, we illustrate the ability to detect RL-producing P. aeruginosa strains with high sensitivity, based on an assay involving phospholipid vesicles encapsulated with a fluorescent dye. This vesicle-lysis assay is confirmed to be solely sensitive to RLs. We illustrate a half maximum concentration for vesicle lysis (EC50) of 40 μM (23.2 μg/mL) using pure commercial RLs and highlight the ability to semi-quantify RLs directly from the culture supernatant, requiring no extra extraction or processing steps or technical expertise. We show that this method is consistent with results from thin-layer chromatography detection and dry weight analysis of RLs but find that the widely used orcinol colorimetric test significantly underestimated RL quantity. Finally, we apply this methodology to compare RL production among strains isolated from either chronic or acute infections. We confirm a positive association between RL production and acute infection isolates (p = 0.0008), highlighting the role of RLs in certain infections.
    Applied Microbiology and Biotechnology 06/2014; 98(16). DOI:10.1007/s00253-014-5904-3 · 3.81 Impact Factor
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    • "2- Heptyl-3-hydroxy-4-quinolone (pseudomonas quinolone signal; PQS), belonging to the family of 2-alkyl-4-quinolones (AQs), was previously described for their antimicrobial activities. Later on, it was found that PQS is integrated within an intricate QS circuit and plays an important role in Pseudomonas aeruginosa pathogenesis by regulating the production of diverse virulence factors including elastase, pyocyanin, and LecA lectin in addition to affecting biofilm formation (Dubern and Diggle, 2008; Heeb et al., 2011). Several other autoinducers like N -(3-oxododecanoyl) homoserine lactone and its tetrameric acid degradation product in Pseudomonas aeruginosa have antibacterial properties against Gram-positive bacteria (Kaufmann et al., 2005). "
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    ABSTRACT: Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic-resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic-resistance in pathogens. In the natural milieu, antibiotics are often found to be present in subinhibitory concentrations acting as signalling molecules supporting quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host-parasite interactions (e.g., phagocytosis, adherence to the target cell and so on). The evolutionary and ecological aspects of antibiotics and antibiotic-resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behaviour of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and genes that confer resistance to antibiotics in nature.
    Frontiers in Microbiology 03/2013; 4:47. DOI:10.3389/fmicb.2013.00047 · 3.94 Impact Factor
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    • "Expression of the seven-gene phenazine biosynthesis (phz) operon is controlled in pseudomonads by homoserine lactone (HSL)-mediated quorum sensing (QS) (Brint and Ohman, 1995; Latifi et al., 1995; Wood and Pierson, 1996; Wood et al., 1997; Chancey et al., 1999; Khan et al., 2005; 2007) and is modulated by numerous transcriptional and translational regulators and small ncRNAs (Haas and Keel, 2003; Haas and Defago, 2005). QS regulation is the most complex in P. aeruginosa , where it consists of two hierarchical HSL-based circuits, Las and Rhl, whose activity is modulated by a third QS system based on 2-heptyl-3-hydroxy-4- quinolone, also known as the Pseudomonas quinolone signal (PQS) (Dubern and Diggle, 2008). In P. fluorescens and P. chlororaphis, QS regulatory genes are situated immediately upstream of the phenazine biosynthesis genes, as opposed to in P. aeruginosa, where las and rhl genes are not directly linked to the two copies of the phz gene cluster. "
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    ABSTRACT: Phenazine compounds represent a large class of bacterial metabolites that are produced by some fluorescent Pseudomonas spp. and a few other bacterial genera. Phenazines were first noted in the scientific literature over 100 years ago, but for a long time were considered to be pigments of uncertain function. Following evidence that phenazines act as virulence factors in the opportunistic human and animal pathogen Pseudomonas aeruginosa and are actively involved in the suppression of plant pathogens, interest in these compounds has broadened to include investigations of their genetics, biosynthesis, activity as electron shuttles, and contribution to the ecology and physiology of the cells that produce them. This minireview highlights some recent and exciting insights into the diversity, frequency and ecological roles of phenazines produced by fluorescent Pseudomonas spp.
    Environmental Microbiology 07/2012; 15(3). DOI:10.1111/j.1462-2920.2012.02846.x · 6.24 Impact Factor
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