Modulation of Gene Expression via Disruption of NF-κB Signaling by a Bacterial Small Molecule

Kravchenko, Vladimir V.; Kaufmann, Gunnar F.; Mathison, John C.; Scott, David A.; Katz, Amnon; Grauer, D.; Lehmann, Malte; Meijler, Michaël M.; Janda, Kim D.; Ulevitch, Richard J.

doi:10.1126/science.1156499

Cited by 195 publications

(223 citation statements)

References 29 publications

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“…Halogenated derivatives of these compounds, however, showed impressive submicromolar activity. Intriguingly, these compounds were also found to inhibit inflammation responses in activated macrophages, reminiscent of the inhibitory activity that 3OC12HSL exhibits on the NF-B pathway (297), which helps to emphasize that bioactive small molecules are capable of targeting several seemingly unrelated pathways. In another study, two novel cyclic depsipeptides were isolated from a marine Photobacterium species and termed solonomides A and B (Table 3); they were identified by screening inhibitory effects against the Staphylococcus aureus agr signaling pathway (141).…”

Section: Natural-product Qs Inhibitorsmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

660

535

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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: Natural-product Qs Inhibitorsmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

660

535

View full text Add to dashboard Cite

show abstract

“…It has been established that the 3-oxo-C12-HSL produced by P. aeruginosa impairs the ability of mammalian cells to respond to the invading bacterial pathogen via the innate immune system (Kravchenko et al, 2008;Kravchenko et al, 2006;Shiner et al, 2006). One of the key steps in this response immediately after receptor-recognition of the pathogen is the activation of the nuclear transcription factor NF-B and consequential expression of genes encoding pro-inflammatory cytokines.…”

Section: Ahl Effect On Human and Plant Cellsmentioning

confidence: 99%

Future research trends in the major chemical language of bacteria

Venturi

Subramoni

2009

HFSP Journal

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“…3OC12-HSL also induces apoptosis in macrophages and neutrophils, suggesting that this molecule not only enhances the expression of virulence genes but also affects immune responses to infection (De Kievit & Iglewski, 2000;Smith et al, 2002;Smith & Iglewski, 2003;Tateda et al, 2003;Telford et al, 1998). Additionally, 3OC12-HSL has been shown to directly affect one of the major regulators of immune responses, NFkB (Kravchenko et al, 2008). …”

Section: Quorum Sensing In Staphylococcus Aureus Virulencementioning

confidence: 99%

Quorum sensing in bacterial virulence

et al. 2010

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Bacteria communicate through the production of diffusible signal molecules termed autoinducers. The molecules are produced at basal levels and accumulate during growth. Once a critical concentration has been reached, autoinducers can activate or repress a number of target genes. Because the control of gene expression by autoinducers is cell-density-dependent, this phenomenon has been called quorum sensing. Quorum sensing controls virulence gene expression in numerous micro-organisms. In some cases, this phenomenon has proven relevant for bacterial virulence in vivo. In this article, we provide a few examples to illustrate how quorum sensing can act to control bacterial virulence in a multitude of ways. Several classes of autoinducers have been described to date and we present examples of how each of the major types of autoinducer can be involved in bacterial virulence. As quorum sensing controls virulence, it has been considered an attractive target for the development of new therapeutic strategies. We discuss some of the new strategies to combat bacterial virulence based on the inhibition of bacterial quorum sensing systems.

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Modulation of Gene Expression via Disruption of NF-κB Signaling by a Bacterial Small Molecule

Cited by 195 publications

References 29 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Future research trends in the major chemical language of bacteria

Quorum sensing in bacterial virulence

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