Cell–cell communication in Gram-negative bacteria

Welch, Martin; Mikkelsen, Helga; Swatton, Jane E.; Smith, Debra; Thomas, Gemma L.; Glansdorp, Freija G.; Spring, David R.

doi:10.1039/b505796p

Cited by 48 publications

(46 citation statements)

References 46 publications

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“…[22] Despite considerable past efforts, potent non-native AHL antagonists of QS remain scarce. [5,7] Further, as the majority of these ligands have only been tested against one bacterial species, the selectivities of non-native AHLs for different R proteins are largely unknown. Insufficient structure-activity relationship (SAR) data for non-native AHLs within and between different Gram negative bacteria have impeded the design of new ligands with improved activities against and selectivities for R proteins.…”

Section: Oxo-octanoyl)-l-homoserine Lactone (Oohl 1) and Trar In Thementioning

confidence: 99%

“…This signaling pathway was first described in the bioluminescent marine symbiont Vibrio fischeri and has been characterized in over 50 different proteobacteria to date. [7,8] Many of these bacteria are clinically, environmentally, and industrially important, perhaps most notably the opportunistic pathogen Pseudomonas aeruginosa, which uses QS to control virulence factor production and growth into drug impervious biofilms. [3] As AHL-R protein binding is an essential event in QS, there has been considerable research on the development of non-native AHLs that can inhibit this ligand-protein interaction.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6] QS is best characterized in the Gram negative proteobacteria, and thus the majority of research on synthetic modulators of QS has focused on these signaling pathways. [5][6][7][8] Proteobacteria use diffusible N-acylated L-homoserine lactones (AHLs) as their primary signaling molecules (Scheme 1); these ligands are produced by AHL synthases (or I proteins) and are sensed by cytoplasmic receptors (or R proteins) that behave as transcription factors. At low cell densities, bacteria constitutively produce the AHL synthase, and thus the AHL ligand, at low levels.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Analyses of N‐Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing

et al. 2008

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Bacterial quorum sensing is mediated by low molecular-weight signals and plays a critical role in both the pathogenesis of infectious disease and beneficial symbioses. There is significant interest in the development of synthetic ligands that can intercept bacterial quorum sensing signals and modulate these outcomes. Here, we report the design and comparative analysis of the effects of ~ 90 synthetic N-acylated homoserine lactones (AHLs) on quorum sensing in three Gram negative bacterial species and a critical examination of the structural features of these ligands that dictate agonistic and antagonistic activity, and selectivity for different R protein targets. These studies have revealed the most comprehensive set of structure-activity relationships to date that direct AHL-mediated quorum sensing and a new set of chemical probes with which to study this complex signaling process. Furthermore, this work provides a foundation on which to design next-generation quorum sensing modulators with improved activities and selectivities.

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Section: Oxo-octanoyl)-l-homoserine Lactone (Oohl 1) and Trar In Thementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Analyses of N‐Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing

et al. 2008

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“…LuxR 유사 단백질들에 의해 각각 수용된다 (Welch et al, 2005;Lee et al, 2006;Schuster and Greenberg, 2006;Jimenez et al, 2012). 또한 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal; PQS)이라는 acyl-HSL과 구분되는 QS 신호물질을 생성 하기도 하는데, 이 신호전달 역시 전체 녹농균의 QS에서 매우 중요한 역할을 담당한다 (Jimenez et al, 2012).…”

Section: Hsl)과 N-buturyl Homoserine Lactone (C4-hsl)이 주로 생성되 며 3oc12unclassified

Analysis of Amino Acid Residues Affecting the Activity of QscR, a Quorum Sensing Receptor of Pseudomonas aeruginosa

Park¹,

Kim²,

Lee

2012

The Korean Journal of Microbiology

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Pseudomonas aeruginosa, a Gram-negative bacterium, is an ubiquitous and opportunistic human pathogen, which expresses many virulence factors through quorum sensing (QS) regulation. QscR, one of the QS signal receptors of P. aeruginosa, has unique features that make it possible to distinguish QscR from other QS receptors. In the present study, we focused on amino acid residues responsible for such a broad signal specificity of QscR. Thus we constructed mutant QscRs: QscRT72I, QscRR132M, and QscRT140I by substituting 72 nd threonine, 132 nd arginine, and 140 th threonine residues with isoleucine, methionine, and isoleucine, respectively by site-directed mutagenesis. When we examined the activity of these mutant QscRs, QscRR132M failed to respond to N-3-oxododecanoyl homoserine lactone (3OC12-HSL), but QscRT72I and QscRT140I remained the ability to respond to 3OC12-HSL despite much reduction of the sensitivity. When we treated a variety of acyl-HSLs with different structure, QscRT72I and QscRT140I showed better responsiveness to N-decanoyl HSL (C10-HSL) or N-dodecanoyl HSL (C12-HSL) that has no oxo-moiety at 3 rd carbon of acyl group than to 3OC12-HSL, and QscRR132M showed no responsiveness to any acyl-HSLs tested here. In addition, QscRT72I and QscRT140I were inhibited by 5f, a QscR inhibitor as similarly as wild type QscR was. These results suggest that while the 130 th arginine is crucial in both activity and acyl-HSL binding of QscR, the 72 nd and 140 th threonines are important in the activity, but they are little responsible for the discrimination of acyl-HSLs or competitive inhibitor.

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“…AHL molecules are used for quorum sensing in many important animal and plant pathogens (10)(11)(12)(13)(14)(15)(16), including Pseudomonas sp. and Agrobacterium tumefaciens, as well as nonpathogenic organisms like the marine bacterium Vibrio fischeri.…”

mentioning

confidence: 99%

Learning the Language of Bacteria

Hodgkinson¹,

Welch

Spring³

2007

ACS Chem. Biol.

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remarkable change to the classical view of the microbial world has become apparent over the last few decades. Rather than bacteria being seen as purely single-celled organisms, existing in isolation, it has become clear that bacteria mainly crowd together in highly complex, multispecies communities. Moreover, they actually "talk" to one another by using small molecules. In Gram-negative bacteria, these small molecules are commonly N-acylated homoserine lactones (AHLs). The design and synthesis of AHL analogues have been performed by many groups (1-8) on a more or less ad hoc basis, making it difficult to draw any firm conclusions about structureactivity relationships and species selectivity. Blackwell and co-workers (9) now report a comprehensive and systematic study that compares the activities of ϳ100 AHL analogues across three species. This not only

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Cell–cell communication in Gram-negative bacteria

Cited by 48 publications

References 46 publications

Comparative Analyses of N‐Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing

Comparative Analyses of N‐Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing

Analysis of Amino Acid Residues Affecting the Activity of QscR, a Quorum Sensing Receptor of Pseudomonas aeruginosa

Learning the Language of Bacteria

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