Gene Network Homology in Prokaryotes Using a Similarity Search Approach: Queries of Quorum Sensing Signal Transduction

Quan, David N.; Bentley, William E.

doi:10.1371/journal.pcbi.1002637

Cited by 23 publications

(26 citation statements)

References 34 publications

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“…Moreover, its signal transduction cascade is evolutionarily extensive and mechanistically diverse (Quan and Bentley, 2012). Hence, one's ability to conceive of and engineer a system for a particular application is substantial when based on AI-2.…”

Section: Introductionmentioning

confidence: 99%

Directed assembly of a bacterial quorum

et al. 2015

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Many reports have elucidated the mechanisms and consequences of bacterial quorum sensing (QS), a molecular communication system by which bacterial cells enumerate their cell density and organize collective behavior. In few cases, however, the numbers of bacteria exhibiting this collective behavior have been reported, either as a number concentration or a fraction of the whole. Not all cells in the population, for example, take on the collective phenotype. Thus, the specific attribution of the postulated benefit can remain obscure. This is partly due to our inability to independently assemble a defined quorum, for natural and most artificial systems the quorum itself is a consequence of the biological context (niche and signaling mechanisms). Here, we describe the intentional assembly of quantized quorums. These are made possible by independently engineering the autoinducer signal transduction cascade of Escherichia coli (E. coli) and the sensitivity of detector cells so that upon encountering a particular autoinducer level, a discretized sub-population of cells emerges with the desired phenotype. In our case, the emergent cells all express an equivalent amount of marker protein, DsRed, as an indicator of a specific QS-mediated activity. The process is robust, as detector cells are engineered to target both large and small quorums. The process takes about 6 h, irrespective of quorum level. We demonstrate sensitive detection of autoinducer-2 (AI-2) as an application stemming from quantized quorums. We then demonstrate sub-population partitioning in that AI-2-secreting cells can 'call' groups neighboring cells that 'travel' and establish a QS-mediated phenotype upon reaching the new locale.

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Section: Introductionmentioning

confidence: 99%

Directed assembly of a bacterial quorum

et al. 2015

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“…AI-2 production has been verified in over 80 species, and AI-2 controls gene expression in a variety of bacteria. By using Local Modular Network Alignment Similarity Tool (LMNAST) to study gene order and generate homologous loci, the AI-2/Lsr system was reported to be phylogenetically more dispersed than the well-studied lac operon, while its distribution remained densest among gammaproteobacteria [64]. These findings together reinforced the hypothesis that bacteria use AI-2 to communicate between species [31,65].…”

Section: Universal Autoinducer Ai-2mentioning

confidence: 77%

Repurposing E. coli by Engineering Quorum Sensing and Redox Genetic Circuits

Wang¹,

Payne²,

Bentley³

2019

Gene Expression and Control

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Because cells have the extraordinary ability to sense and respond to even subtle environmental changes by intricately regulating their gene expression patterns, their behaviors can be intentionally "tuned" by altering the state of their environments in a prescribed or rational manner. Rational control of both external and internal molecular stimuli provides a basis for many biotechnological applications including the expression of foreign protein products. This is done by coordinately controlling product synthesis while retaining the cell in a productive state. Quorum sensing (QS), a molecular signaling modality that mediates cell-cell communication, autonomously facilitates both inter-and intra-species gene regulation. This process can be rewired to enable autonomously actuated, but molecularly programmed, genetic control. Recently, even electrical signals, which have long been used to control the most sophisticated of man-made devices, are now employed to alter cell signaling processes enabling computer programmed behavior, particularly in cells suitably engineered to accommodate electrical signals. By minimally engineering these genetic circuits, new applications have emerged for the repurposing of Escherichia coli, from creating innovative sensor concepts to stimulating the emerging field of electrogenetics.Gene Expression and Control 2 as well as the extracellular microenvironmental state in the vicinity of 'designer' production strains in order to program gene expression and behavior. These techniques incorporate the understanding of cell metabolism and the transcriptome, cell-cell communication (previously reviewed by [2,3]), and biological redox reactions (previously reviewed by [4]). This chapter will mainly focus on recent advances in how actuation of genes is accomplished in Escherichia coli through methods that require only minimal genetic rewiring and the technologies developed on such platforms, for instance those of biosensors and bioelectric devices.

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“…Here, we target autoinducer‐2 (AI‐2) by the incorporation of a natural enzyme that modifies the autoinducer to its phosphorylated form, preventing its uptake (Kamaraju et al, ) into bacteria that employ the Lsr signal transduction cascade (Quan & Bentley, ; Roy et al, ). AI‐2 was chosen for several reasons: it is used in signaling among Gram‐positive and Gram‐negative bacteria (Pereira et al, ; Quan & Bentley, ), it is not produced by eukaryotic cells (Vendeville, Winzer, Heurlier, Tang, & Hardie, ) and apparently has minimal effect on gastrointestinal epithelial cells (Zargar, Quan, Carter, et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Here, we target autoinducer-2 (AI-2) by the incorporation of a natural enzyme that modifies the autoinducer to its phosphorylated form, preventing its uptake (Kamaraju et al, 2011) into bacteria that employ the Lsr signal transduction cascade (Quan & Bentley, 2012;Roy et al, 2009). AI-2 was chosen for several reasons: it is used in signaling among Gram-positive and Gram-negative bacteria (Pereira et al, 2013;Quan & Bentley, 2012), it is not produced by eukaryotic cells (Vendeville, Winzer, Heurlier, Tang, & Hardie, 2005) and apparently has minimal effect on gastrointestinal epithelial cells (Zargar, Quan, Carter, et al, 2015). Also, the mechanism of AI-2 phosphorylation is relatively well understood (Zhu, Hixon, Globisch, Kaufmann, & Janda, 2013) and previous work has demonstrated that interfering with AI-2 can alter QS communication in "synthetic ecosystems" (Roy, Adams, & Bentley, 2011;Roy et al, 2009Roy et al, , 2010 or otherwise influence biofilm formation and clearance when used in combination with antibiotics (Roy et al, 2013).…”

mentioning

confidence: 99%

Incorporating LsrK AI‐2 quorum quenching capability in a functionalized biopolymer capsule

Rhoads

Hauk

Terrell

et al. 2017

Biotech & Bioengineering

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Antibacterial resistance is an issue of increasing severity as current antibiotics are losing their effectiveness and fewer antibiotics are being developed. New methods for combating bacterial virulence are required. Modulating molecular communication among bacteria can alter phenotype, including attachment to epithelia, biofilm formation, and even toxin production. Intercepting and modulating communication networks provide a means to attenuate virulence without directly interacting with the bacteria of interest. In this work, we target communication mediated by the quorum sensing (QS) bacterial autoinducer-2, AI-2. We have assembled a capsule of biological polymers alginate and chitosan, attached an AI-2 processing kinase, LsrK, and provided substrate, ATP, for enzymatic alteration of AI-2 in culture fluids. Correspondingly, AI-2 mediated QS activity is diminished. All components of this system are "biofabricated"-they are biologically derived and their assembly is accomplished using biological means. Initially, component quantities and kinetics were tested as assembled in microtiter plates. Subsequently, the identical components and assembly means were used to create the "artificial cell" capsules. The functionalized capsules, when introduced into populations of bacteria, alter the dynamics of the AI-2 bacterial communication, attenuating QS activated phenotypes. We envision the assembly of these and other capsules or similar materials, as means to alter QS activity in a biologically compatible manner and in many environments, including in humans.

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Gene Network Homology in Prokaryotes Using a Similarity Search Approach: Queries of Quorum Sensing Signal Transduction

Cited by 23 publications

References 34 publications

Directed assembly of a bacterial quorum

Directed assembly of a bacterial quorum

Repurposing E. coli by Engineering Quorum Sensing and Redox Genetic Circuits

Incorporating LsrK AI‐2 quorum quenching capability in a functionalized biopolymer capsule

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