Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control

Rutherford, Steven T.; Bassler, Bonnie L.

doi:10.1101/cshperspect.a012427

Cited by 1,635 publications

(1,348 citation statements)

References 256 publications

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“…Q uorum sensing is a process of bacterial communication used to collectively control group behaviors (1,2). This process relies on the production, release, and group-wide detection of signal molecules called autoinducers, which in gram-negative bacteria are typically homoserine lactones (HSLs) (1,2).…”

mentioning

confidence: 99%

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

O’Loughlin

Miller²,

Siryaporn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

659

550

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Quorum sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling quorum-sensing circuits with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Here, we analyze synthetic molecules for inhibition of the two P. aeruginosa quorum-sensing receptors, LasR and RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both the production of the virulence factor pyocyanin and biofilm formation. mBTL also protects Caenorhabditis elegans and human lung epithelial cells from killing by P. aeruginosa. Both LasR and RhlR are partially inhibited by mBTL in vivo and in vitro; however, RhlR, not LasR, is the relevant in vivo target. More potent antagonists do not exhibit superior function in impeding virulence. Because LasR and RhlR reciprocally control crucial virulence factors, appropriately tuning rather than completely inhibiting their activities appears to hold the key to blocking pathogenesis in vivo.

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mentioning

confidence: 99%

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

O’Loughlin

Miller²,

Siryaporn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

659

550

View full text Add to dashboard Cite

show abstract

“…In many bacteria, these decisions are aided by the secretion and detection of small diffusible molecules, in a process called quorum sensing (QS) (2,3). QS controls a variety of traits, including pathogen virulence (3) leading to "QS interference" (2-6) emerging as a control strategy for several bacterial pathogens.…”

mentioning

confidence: 99%

Combinatorial quorum sensing allows bacteria to resolve their social and physical environment

Cornforth

Popat

McNally

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

173

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Quorum sensing (QS) is a cell-cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay between its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic "AND-gate" responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication.diffusion sensing | bacterial signaling | efficiency sensing | collective behavior | bacterial cooperation

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“…Since then, researchers have observed this 'quorum-sensing' behaviour in many species [2][3][4] and have started to decipher the biochemistry and genetics of how it happens 5 . They have also been developing devices with which to characterize the messages that are transmitted and received.…”

Section: Technology Featurementioning

confidence: 99%

Stop the microbial chatter

Marx¹

2014

Nature

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Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control

Cited by 1,635 publications

References 256 publications

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

Combinatorial quorum sensing allows bacteria to resolve their social and physical environment

Stop the microbial chatter

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