Manipulation of Bacterial Signaling Using Engineered Histidine Kinases

Kowallis, Kimberly A.; Duvall, Samuel W.; Zhao, Wei; Childers, W. Seth

doi:10.1007/978-1-4939-9884-5_10

Cited by 5 publications

(8 citation statements)

References 93 publications

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“… What are the design principles of sensor HKs? How sensor HKs may be efficiently employed in the generation of new molecular biology tools, including artificial sensors [ 16 , 17 , 18 ] and reporters [ 15 , 22 ]? …”

Section: Discussionmentioning

confidence: 99%

“…Since many of them are important for bacterial survival and pathogenicity, TCS constitute promising targets for antimicrobial treatments [ 12 , 13 , 14 ]. TCS receptors are also often used in synthetic biology, in engineered proteins and cellular networks [ 15 , 16 , 17 , 18 , 19 ], as well as whole cell biosensors [ 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity

Gushchin

Aleksenko

Orekhov

et al. 2021

IJMS

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Under anaerobic conditions, bacteria may utilize nitrates and nitrites as electron acceptors. Sensitivity to nitrous compounds is achieved via several mechanisms, some of which rely on sensor histidine kinases (HKs). The best studied nitrate- and nitrite-sensing HKs (NSHKs) are NarQ and NarX from Escherichia coli. Here, we review the function of NSHKs, analyze their natural diversity, and describe the available structural information. In particular, we show that around 6000 different NSHK sequences forming several distinct clusters may now be found in genomic databases, comprising mostly the genes from Beta- and Gammaproteobacteria as well as from Bacteroidetes and Chloroflexi, including those from anaerobic ammonia oxidation (annamox) communities. We show that the architecture of NSHKs is mostly conserved, although proteins from Bacteroidetes lack the HAMP and GAF-like domains yet sometimes have PAS. We reconcile the variation of NSHK sequences with atomistic models and pinpoint the structural elements important for signal transduction from the sensor domain to the catalytic module over the transmembrane and cytoplasmic regions spanning more than 200 Å.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity

Gushchin

Aleksenko

Orekhov

et al. 2021

IJMS

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“…A TCS consists of a histidine kinase (HK) and a response regulator (RR), which are responsible for sensing environmental signals and regulating cellular processes, respectively (Figure 1A). TCSs are promising targets for engineering biosensors for four reasons 26 .…”

Section: Introductionmentioning

confidence: 99%

A Biosensor for Detection of Indole Metabolites

Wang¹,

Zhang²,

Childers³

2021

Preprint

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The lack of diverse health-related biosensors limits the progress towards our understanding of how the microbiome metabolism impacts health. Microbially produced indole-3-aldehyde (I3A) has been associated with reducing inflammation in diseases such as ulcerative colitis by stimulating the aryl hydrocarbon receptor (AhR) pathway. We mined the protein database for sensors of gut microbiome metabolites and developed a biosensor for I3A. We engineered E. coli embedded with a single plasmid carrying a chimeric two-component system that detects I3A. Our I3A receptor characterization identified residues that contribute to high specificity of the sensor in a range of 0.1-10 μM. The I3A biosensor opens the door to sensing indole metabolites produced at the host-microbe interface and provides new parts for synthetic biology applications.

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“…A TCS consists of a histidine kinase (HK) and a response regulator (RR), which are responsible for sensing environmental signals and regulating cellular processes, respectively (Figure A). TCSs are promising targets for engineering biosensors for three reasons …”

mentioning

confidence: 99%

“…TCSs are promising targets for engineering biosensors for three reasons. 27 First, TCSs provide a warehouse of sensors, 28 including pH, metals, quorum sensing compounds, and secondary metabolites. For instance, TCSs sensing a broad spectrum of light and have been leveraged as optogenetic tools in E. coli.…”

mentioning

confidence: 99%

A Biosensor for Detection of Indole Metabolites

2021

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Microbially produced indole metabolites serve as a diverse family of interspecies and interkingdom signaling molecules in the context of human health, crop production, and antibiotic resistance. We mined the protein database for sensors of indole metabolites and developed a biosensor for indole-3-aldehyde (I3A). Microbially produced I3A has been associated with reducing inflammation in diseases such as ulcerative colitis by stimulating the aryl hydrocarbon receptor pathway. We engineered an E. coli strain embedded with a single plasmid carrying a chimeric two-component system that detects I3A. Our I3A receptor characterization confirmed binding site residues that contribute to the sensor's I3A detection range of 0.1−10 μM. This new I3A biosensor opens the door to sensing indole metabolites produced at various host−microbe interfaces and provides new parts for synthetic biology applications.

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Manipulation of Bacterial Signaling Using Engineered Histidine Kinases

Cited by 5 publications

References 93 publications

Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity

Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity

A Biosensor for Detection of Indole Metabolites

A Biosensor for Detection of Indole Metabolites

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