New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing

Reverchon, Sylvie; Chantegrel, Bernard; Deshayes, Christian; Doutheau, Alain; Hugouvieux‐Cotte‐Pattat, Nicole

doi:10.1016/s0960-894x(02)00124-5

Cited by 128 publications

(101 citation statements)

References 18 publications

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Section: Interference With the Signal Receptormentioning

confidence: 99%

“…If the size of the substituent is increased beyond that of a phenyl group, the antagonistic effect is lost. As the size difference of the cyclic alkyls and the aryl substituents is minimal, it is hypothesized that the aryl compounds can interact with aromatic amino acid residues in the LuxR protein, preventing normal activation (Reverchon et al, 2002). The QSI effect of the aryl AHLs can be further enhanced by replacing the C-1 carbonyl group of the side chain with a sulphonyl group (Castang et al, 2004).…”

Section: Interference With the Signal Receptormentioning

confidence: 99%

“…A similar observation was made with other compounds and QS systems. A hexane ring carrying a 3-oxo-C6 side chain showed agonistic properties, whereas antagonism was observed with a compound having the 3-oxo-C6 side chain attached to a phenyl ring (Smith et al, 2003b;Reverchon et al, 2002).QSIs have also been identified by screening of random compound libraries. Using the above-mentioned QSIS screens, Rasmussen et al (2005a) identified several QSI compounds with structures unrelated to the signal molecules, including 4-nitro-pyridine-N-oxide (4-NPO), indole, p-benzoquinone, 2,4,5-tribromoimidazole, indole and 3-nitrobenzene sulphone amide, the first being the most effective.…”

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Quorum sensing inhibitors: a bargain of effects

2006

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Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In Pseudomonas aeruginosa, QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host innate immune system. Therefore, QS is an obvious target for a novel class of antimicrobial drugs which would function to efficiently block reception of the cognate QS signals in vivo, and thereby be capable of inducing chemical attenuation of pathogens. As QS is not directly involved in processes essential for growth of the bacteria, inhibition of QS does not impose harsh selective pressure for development of resistance as with antibiotics. Numerous chemical libraries of both natural and synthetic origin have been screened and several QS-inhibitory compounds have been identified. In animal pulmonary infection models, such inhibitors have proven able to significantly improve clearing of the infecting bacteria and reduce mortality. In addition, several enzymes that are able to inactivate the bacterial QS signal molecules have been identified. This inactivation leads to blockage of QS-mediated virulence of plant pathogens in several models. Quorum sensingBacteria are social organisms capable of interacting with each other and their surroundings. Particularly well described is the ability to coordinate gene expression in accordance with population density, a process termed quorum sensing (QS) (Fuqua et al., 1994). In Gram-negative bacteria this is achieved by production and reception of diffusible signal molecules in the form of acylhomoserine lactones (AHLs) (Fig. 1). The signal molecules are produced by an AHL synthase encoded by homologues of the AHL synthase gene luxI, which was first identified in Vibrio fischeri (Engebrecht & Silverman, 1984). At low population densities, luxI is constitutively expressed at a low, basal level. Hence, the AHLs accumulate in the surroundings. The LuxR family of receptor/response regulator proteins perceives the AHLs. At a certain threshold concentration of AHL, the signal molecule forms a complex with the receptor protein, which becomes activated. The activated receptor-signal complex in turn forms dimers or multimers with other activated LuxR-AHL complexes. These dimers or multimers function as transcriptional regulators controlling expression of QS-regulated target genes. The QS paradigm states that transcription of QS target genes is activated at a certain population density (which is proportional to the AHL concentration) known as the 'quorum size' -the number of bacteria required to activate the QS system (Eberl, 1999;Fuqua et al., 1994;Salmond et al., 1995;Parsek et al., 1999). In Pseudomonas aeruginosa, however, recent research has shown that each individual QS-regulated gene possesses its own specific quorum size. There is not a single population density at which all QS genes are activated; rather, different genes are activated at different population densities Wagner et al....

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Section: Interference With the Signal Receptormentioning

confidence: 99%

Section: Interference With the Signal Receptormentioning

confidence: 99%

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confidence: 99%

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Quorum sensing inhibitors: a bargain of effects

2006

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“…Other natural compounds inhibiting QS have been found in garlic extracts and in members of the genus Penicillium (Gonzalez and Keshavan, 2006;Rasmussen et al, 2005a;Rasmussen et al, 2005b). Synthetic AHL analogs have and are currently being studied for their behavior in affecting QS systems; however, thus far they appear to be less effective than the natural compounds (Gonzalez and Keshavan, 2006;Olsen et al, 2002;Reverchon et al, 2002).…”

Section: Practical Applications In the Control Of Bacterial Ahl Quorumentioning

confidence: 99%

Future research trends in the major chemical language of bacteria

Venturi

Subramoni

2009

HFSP Journal

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“…Modification of the side chain has also yielded many active compounds. For example, various structures based on 5 with a substituted aryl side chain showed strong inhibition (typically 50% inhibition at 2-10 M) of quorum sensing in V. fischeri (21).…”

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Making Bacteria Behave: New Agonists and Antagonists of Quorum Sensing

Pomianek

Semmelhack

2007

ACS Chem. Biol.

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Small-molecule agonists and antagonists of bacterial quorum sensing can enhance our understanding of this form of cell–cell communication. A recent effort has discovered effective modulators of the autoinducer-1 circuit for bacterial quorum sensing by the synthesis and evaluation of a small library of aryl-substituted acyl-homoserine lactone analogues. This series highlights the sensitivity to structure of the contrasting responses of agonism and antagonism of the natural signal and identifies an analogue that provokes the same response as the natural signal but at 10-fold lower concentration, a “superagonist”.

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New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing

Cited by 128 publications

References 18 publications

Quorum sensing inhibitors: a bargain of effects

Quorum sensing inhibitors: a bargain of effects

Future research trends in the major chemical language of bacteria

Making Bacteria Behave: New Agonists and Antagonists of Quorum Sensing

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