LuxR dependent quorum sensing inhibition by N,N′-disubstituted imidazolium salts

Sabbah, Mohamad; Soulère, Laurent; Reverchon, Sylvie; Queneau, Yves; Doutheau, Alain

doi:10.1016/j.bmc.2011.06.075

Cited by 16 publications

(13 citation statements)

References 47 publications

(50 reference statements)

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“…Such high-throughput screening has also led to the identification of two classes of molecules able to suppress V. cholerae virulence factor expression through modulation of either the noncanonical AHL receptor LuxN or the NtrC-like response regulator LuxO (189). Additionally, structure-based derivatiza-tion of previously identified antagonists has led to the discovery of multiple non-AHL pharmacophores with activity against LuxRtype proteins, including disubstituted imidazolium salts (183,190) and N-acyl cyclopentylamides (191,192).…”

Section: Inhibition Of Signal Detection Synthetic Signal Analogues Anmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

690

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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Section: Inhibition Of Signal Detection Synthetic Signal Analogues Anmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

690

556

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“…Additionally, AHL acylases, initially discovered in Variovorax paradoxus, have also been found in other bacteria and degrade AHL by hydrolyzing the amide linkage (36)(37)(38)(39). In addition to these examples, a series of AHL analogues with varying side chain lengths and substitutions have been synthesized de novo and are highly effective in inhibiting the QS systems of several Gram-negative bacteria (30,(40)(41)(42)(43)(44). The few known ex- …”

mentioning

confidence: 99%

Novel Reporter for Identification of Interference with Acyl Homoserine Lactone and Autoinducer-2 Quorum Sensing

Weiland‐Bräuer

Pinnow

Schmitz

2015

Appl Environ Microbiol

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Two reporter strains were established to identify novel biomolecules interfering with bacterial communication (quorum sensing [QS]). The basic design of these Escherichia coli-based systems comprises a gene encoding a lethal protein fused to promoters induced in the presence of QS signal molecules. Consequently, these E. coli strains are unable to grow in the presence of the respective QS signal molecules unless a nontoxic QS-interfering compound is present. The first reporter strain designed to detect autoinducer-2 (AI-2)-interfering activities (AI2-QQ.1) contained the E. coli ccdB lethal gene under the control of the E. coli lsrA promoter. The second reporter strain (AI1-QQ.1) contained the Vibrio fischeri luxI promoter fused to the ccdB gene to detect interference with acyl-homoserine lactones. Bacteria isolated from the surfaces of several marine eukarya were screened for quorum-quenching (QQ) activities using the established reporter systems AI1-QQ.1 and AI2-QQ.1. Out of 34 isolates, two interfered with acylated homoserine lactone (AHL) signaling, five interfered with AI-2 QS signaling, and 10 were demonstrated to interfere with both signal molecules. Open reading frames (ORFs) conferring QQ activity were identified for three selected isolates (Photobacterium sp., Pseudoalteromonas sp., and Vibrio parahaemolyticus). Evaluation of the respective heterologously expressed and purified QQ proteins confirmed their ability to interfere with the AHL and AI-2 signaling processes. Q uorum sensing (QS) is the cell-cell communication betweenbacteria that allows the perception of population density by small signaling molecules-so-called autoinducers-and modifies gene expression in response to the population density. It controls a wide spectrum of processes and phenotypic behaviors, including stress resistance, production of toxins and secondary metabolites, pathogenicity, swarming, and biofilm formation (for a review, see references 1 and 2). In addition to playing important roles in intraspecies and interspecies communication, QS is also involved in host-microbe interactions (3-5). Intraspecific communication of Gram-negative bacteria is based on the production and perception of acylated homoserine lactones (AHLs) synthesized by LuxI homologs. Increasing intracellular concentrations of diffusible AHLs with higher cell densities are perceived by binding of the AHLs to the cognate receptor (e.g., LuxR in Vibrio fischeri), resulting in activation or inhibition of target gene transcription (6, 7). Interspecific communication between different species within one habitat has been demonstrated to depend on the synthesis and detection of the universal autoinducer-2 (AI-2), which can be inhibited by furanones (8, 9). The perception of these signal molecules is achieved either by a two-component regulatory system (e.g., in Vibrio harveyi, where the induced phosphorylation cascade finally results in the induction of specific target genes) (10), or by transportation of the signal molecule into the cell (e.g., in Escherichia coli,...

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“…Both substitutions were found to influence the QSI activity when tested in a modified E. coli strain which expresses the Vibrio fisheri QS-system. Indeed, a stronger QSI-activity was found for shorter chains when the aromatic residue was larger (highly halogenated), or for longer chains when the aromatic residue was smaller (unsubstituted or sterically constrained) [22]. …”

Section: Resultsmentioning

confidence: 99%

“…The library includes various types of QS agonists or antagonists, either structurally related to AHL (carboxamides, sulfonamides, urea, sulfonylurea, reverse amides, triazoles or tetrazoles), or bromoenamines and bromofuranones designed by analogy to natural compounds known as QSI [24–31]. This latter category includes the imidazolium derivatives found to be active in this study and designed as analogues of calmidazolium which were identified as QSIs by virtual ( in silico ) screening [21,22]. …”

Section: Methodsmentioning

confidence: 99%

N,N’-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers

Essarts

Sabbah

Comte

et al. 2013

IJMS

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Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs targeting the virulence of Pectobacterium. Four N,N′-bisalkylated imidazolium salts were identified as QSIs; they were active at the μM range. In potato tuber assays, two of them were able to decrease the severity of the symptoms provoked by P. atrosepticum. This work extends the range of the QSIs acting on the Pectobacterium-induced soft-rot disease.

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LuxR dependent quorum sensing inhibition by N,N′-disubstituted imidazolium salts

Cited by 16 publications

References 47 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Novel Reporter for Identification of Interference with Acyl Homoserine Lactone and Autoinducer-2 Quorum Sensing

N,N’-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers

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