Census of solo LuxR genes in prokaryotic genomes

Hudaiberdiev, Sanjarbek; Choudhary, Kumari Sonal; Alvarez, Roberto Vera; Gelencsér, Zsolt; Ligeti, Balázs; Lamba, Doriano; Pongor, Sándor

doi:10.3389/fcimb.2015.00020

Cited by 70 publications

(56 citation statements)

References 26 publications

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“…Approximately 76% of annotated LuxR proteins belong to the so-called LuxR-solo class of transcription factors 70 , that is, they have no accompanying LuxI synthases. This suggests that many more autoinducers could exist that are produced by non-LuxI synthases or that are supplied by other bacteria and modulate the activity of these receptors.…”

Section: Autoinducers Receptors and Specificitymentioning

confidence: 99%

Quorum sensing signal–response systems in Gram-negative bacteria

2016

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/ Preface Bacteria use quorum sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of quorum sensing signal–response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host–microbial associations and antibacterial therapy.

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Section: Autoinducers Receptors and Specificitymentioning

confidence: 99%

Quorum sensing signal–response systems in Gram-negative bacteria

2016

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“…Recent efforts to catalogue solo luxR genes indicate that many of the LuxR proteins identified feature multiple conserved cysteines, particular in their LBDs, and it has been postulated that these cysteines, including Cys 79 in solo LuxR proteins, are positioned well for disulfide bond formation and possible redox regulation (42). Based on prior reports (15) and our studies, it is certainly conceivable that LasR Cys 79 has an important role in vivo as a reactive thiol, particularly in poorly folded LasR, and continued work will enable a full understanding of this residue.…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights into the Impact of Oxidative Stress on the Quorum-Sensing Regulator Protein LasR

Kafle¹,

Amoh²,

Reaves³

et al. 2016

Journal of Biological Chemistry

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The LasR regulator protein functions at the top of the Pseudomonas aeruginosa quorum-sensing hierarchy and is implicated in promoting bacterial virulence. Of note is recent evidence that this transcription factor may also respond to oxidative stress. Here, all cysteines in LasR were inspected to deduce their redox sensitivity and to probe the connection between stress response and LasR activity using purified LasR and individual LasR domains. Cys 79 in the ligand binding domain of LasR appears to be important for ligand recognition and folding of this domain to potentiate DNA binding but does not seem to be sensitive to oxidative stress when bound to its native ligand. Two cysteines in the DNA binding domain of LasR do form a disulfide bond when treated with hydrogen peroxide, and formation of this Cys 201 -Cys 203 disulfide bond appears to disrupt the DNA binding activity of the transcription factor. Mutagenesis of either of these cysteines leads to expression of a protein that no longer binds DNA. A cell-based reporter assay linking LasR function with ␤-galactosidase activity gave results consistent with those obtained with purified LasR. This work provides a possible mechanism for oxidative stress response by LasR and indicates that multiple cysteines within the protein may prove to be useful targets for disabling its activity.The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic human pathogen that establishes chronic infections in immunocompromised patients, with persistent pulmonary colonization in individuals with cystic fibrosis (1-3). Like many bacteria, P. aeruginosa employs quorumsensing (QS) 4 machinery to communicate local population density through the exchange of self-produced signaling molecules (4). QS contributes to the development of acute infections by coordinating the production of multiple virulence factors, including elastase and pyocyanin, and the formation of biofilms (5-7). QS in P. aeruginosa is largely mediated by N-acyl L-homoserine lactone autoinducer molecules, biosynthesized by LuxI-type synthases, and detected by LuxR-type regulator proteins (8). The two major systems responsive to acylhomoserine lactones (AHLs) in P. aeruginosa are LasI/LasR and RhlI/RhlR. LasI and RhlI are LuxI-type synthases, whereas LasR and RhlR are LuxR-type regulatory proteins. These AHL-dependent systems are also closely connected to signaling governed by 2-alkyl-4-quinolones in P. aeruginosa (9).The regulator protein LasR, with its cognate synthase LasI, functions at the top of the P. aeruginosa quorum-sensing hierarchy (10). Like other LuxR-type proteins, this transcription factor is composed of two domains (11). The amino-terminal ligand binding domain (LBD) specifically recognizes its autoinducer, N-(3-oxo-dodecanoyl)-L-homoserine lactone (3O-C 12 -HSL), promoting protein folding and dimerization, whereas the DNA binding domain (DBD) recognizes target sites to activate downstream gene expression. There has been significant interest in understanding LasR, as its inhibition represents a...

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“…Crosstalk between species of quorum sensing bacteria is prevalent in nature as well. Environmental bacteria can respond to HSLs produced by other species for both cooperative and competitive gains [24][25][26] . The generation and disposal of large quantities of HSLs could cause misregulation of quorum sensing within microbial niches.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Diverse Homoserine Lactone Synthases inEscherichia coli

Daer

Barrett

Melendez

et al. 2018

Preprint

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Quorum sensing networks have been identified in over one hundred bacterial species to date . A subset of these networks regulate group behaviors, such as bioluminescence, virulence, and biofilm formation, by sending and receiving small molecules called homoserine lactones (HSLs). Bioengineers have incorporated quorum sensing pathways into genetic circuits to connect logical operations. However, the development of higher-order genetic circuitry is inhibited by crosstalk, in which one quorum sensing network responds to HSLs produced by a different network. Here, we report the construction and characterization of a library of ten synthases including some that are expected to produce HSLs that are incompatible with the Lux pathway, and therefore show no crosstalk. We demonstrated their function in a common lab chassis, Escherichia coli BL21, and in two contexts, liquid and solid agar cultures, using decoupled Sender and Receiver pathways. We observed weak or strong stimulation of a Lux Receiver by longer-chain or shorter-chain HSL-generating Senders, respectively. We also considered the under-investigated risk of unintentional release of incompletely deactivated HSLs in biological waste. We found that HSL-enriched media treated with bleach is still bioactive, while autoclaving deactivates LuxR induction. This work represents the most extensive comparison of quorum sensing synthases to date and greatly expands the bacterial signaling toolkit while recommending practices for disposal based on empirical, quantitative evidence.

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Census of solo LuxR genes in prokaryotic genomes

Cited by 70 publications

References 26 publications

Quorum sensing signal–response systems in Gram-negative bacteria

Quorum sensing signal–response systems in Gram-negative bacteria

Molecular Insights into the Impact of Oxidative Stress on the Quorum-Sensing Regulator Protein LasR

Characterization of Diverse Homoserine Lactone Synthases inEscherichia coli

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