Bacterial Sensor Research Articles

How does Quorum Sensing of Intestinal Bacteria Affect Our Health and Mental Status?

The human gut is host to almost 3000 microbial species, of which 90% are bacteria. Quorum sensing (QS) molecules generated by intestinal bacteria are important in establishing species- and strain-level structures within the gut microbiome but are also used to communicate with the host. Although we do not know which QS molecules have the most direct interaction with intestinal and sensory neurons, it is clear they affect our physiological and mental health. Signals produced by bacteria are diverse and include autoinducers (AIs), homoserine lactones (HSLs), quinolines, peptides, toxins and proteases. These signaling molecules activate specific receptors in the bacterial cell wall and trigger sensors in the cytoplasm that regulate gene expressions. A better understanding of the gene structures encoding the production of QS molecules is of importance when selecting strains with neurogenerative and other probiotic properties. Furthermore, QS molecules may be used as biomarkers in the diagnosis of inflammable bowel disease (IBD), irritable bowel syndrome (IBS) and colorectal cancer (CRC). In the future, it should be possible to use QS biomarkers to diagnose neurological and psychiatric diseases such as anxiety and depression, major depressive disorder (MDD), schizophrenia, bipolar disorder, autism and obsessive-compulsive disorder (OCD).

NIN-like protein 7 transcription factor is a plant nitrate sensor.

Nitrate is an essential nutrient and signaling molecule for plant growth. Plants sense intracellular nitrate to adjust their metabolic and growth responses. Here we identify the primary nitrate sensor in plants. We found that mutation of all seven Arabidopsis NIN-like protein (NLP) transcription factors abolished plants' primary nitrate responses and developmental programs. Analyses of NIN-NLP7 chimeras and nitrate binding revealed that NLP7 is derepressed upon nitrate perception via its amino terminus. A genetically encoded fluorescent split biosensor, mCitrine-NLP7, enabled visualization of single-cell nitrate dynamics in planta. The nitrate sensor domain of NLP7 resembles the bacterial nitrate sensor NreA. Substitutions of conserved residues in the ligand-binding pocket impaired the ability of nitrate-triggered NLP7 to control transcription, transport, metabolism, development, and biomass. We propose that NLP7 represents a nitrate sensor in land plants.

Comparative Analysis of Cell Metabolic Activity Sensing by Escherichia coli rrnB P1-lux and Cd Responsive-Lux Biosensors: Time-Resolved Experiments and Mechanistic Modelling

Whole-cell bacterial sensors are used in medical/environmental applications to detect chemicals, and to assess medium toxicity or stress. Non-specific constitutive biosensors generally serve the latter purpose, whereas chemical detection is performed with biosensors involving a specific chemical-inducible promoter. Herein, we show that functioning principles of specific and non-specific whole-cell biosensors are not exclusive as both can probe modulations of cell metabolic activity under stressing conditions. The demonstration is based on (i) time-resolved measurements of bioluminescence produced by constitutive rrnB P1-luxCDABE Escherichia coli biosensor in media differing with respect to carbon source, (ii) theoretical reconstruction of the measured signals using a here-reported theory for bioluminescence generated by constitutive cells, (iii) comparison between time-dependent cell photoactivity (reflecting metabolic activity) retrieved by theory with that we reported recently for cadmium-inducible PzntA-luxCDABE E. coli in media of similar compositions. Whereas signals of constitutive and non-constitutive biosensors differ in terms of shape, amplitude and peak number depending on nutritional medium conditions, analysis highlights the features shared by their respective cell photoactivity patterns mediated by the interplay between stringent response and catabolite repressions. The work advocates for the benefits of a theoretical interpretation for the time-dependent response of biosensors to unravel metabolic and physicochemical contributions to the bioluminescence signal.

Cascade signal enhancement by integrating DNA walking and RCA reaction-assisted “silver-link” crossing electrode for ultrasensitive electrochemical detection of Staphylococcus aureus

The key factor to control the incidence rate of diseases caused by bacteria is rapid detection and early diagnosis. Herein, we proposed a new electrochemical bacterial sensor by coupling DNA walking and rolling circle amplification (RCA) reaction-assisted “silver-link” crossing electrode. Staphylococcus aureus (S. aureus) was detected using this proof-of concept strategy. Aptamer/DNA walker and auxiliary sequence (AS)/RCA reaction probe (RP) duplexes were modified on the electrode surface. The binding of S. aureus with its aptamer caused the disintegration of aptamer/DNA walker and released DNA walker. With the help of Exo III, DNA walker moved along the electrode surface and AS in AS/RP duplex was continuously digested to release RP. By introducing phi29 DNA polymerase, RCA reaction was performed using RP as the reaction primer to form long single-strand RCA extension products between the electrodes. The “silver-link” crossing electrode was formed by metallization of “gene-link”, significant conductivity was thus acquired for bacteria detection. The limit of detection (LOD) was 10 CFU/mL and detection time was 2 h. The proposed sensor has high efficiency, good stability and low background signal, human serum and milk samples were successfully detected, which emerged a promising potential in the food monitoring and clinical diagnosis.

Microfluidic-Based Bacterial Molecular Computing on a Chip

Biocomputing systems based on engineered bacteria can lead to novel tools for environmental monitoring and detection of metabolic diseases. In this paper, we propose a Bacterial Molecular Computing on a Chip (BMCoC) using microfluidic and electrochemical sensing technologies. The computing can be flexibly integrated into the chip, but we focus on engineered bacterial AND Boolean logic gate and ON-OFF switch sensors that produces secondary signals to change the pH and dissolved oxygen concentrations. We present a prototype with experimental results that shows the electrochemical sensors can detect small pH and dissolved oxygen concentration changes created by the engineered bacterial populations’ molecular signals. Additionally, we present a theoretical model analysis of the BMCoC computation reliability when subjected to unwanted effects, i.e., molecular signal delays and noise, and electrochemical sensors threshold settings that are based on either standard or blind detectors. Our numerical analysis found that the variations in the production delay and the molecular output signal concentration can impact on the computation reliability for the AND logic gate and ON-OFF switch. The molecular communications of synthetic engineered cells for logic gates integrated with sensing systems can lead to a new breed of biochips that can be used for numerous diagnostic applications.

Association between NOD2 and autoinflammation presenting as Yellow Nail Syndrome

Background: Yellow Nail Syndrome is defined as a triad of lymphedema, respiratory symptoms, and nail discolouration. The precise etiology remains unknown, however it has been reported alongside a broad spectrum of conditions including malignancies, autoinflammatory diseases, and immunodeficiencies. Aim: To highlight the association between defects in the intracellular bacterial sensor gene NOD2 and Yellow Nail Syndrome. Methods: A retrospective review of the patient’s chart was performed, including family history, characteristics, immune laboratory evaluation, and genetics. Results: A 65-year-old female was referred to our centre for lymphedema and bronchiectasis. She had recurrent episodes of pneumonia, cellulitis, and oral ulcers. Bilateral lymphedema on her lower limbs up to the hip and discoloured yellow nails were reported. Given her clinical picture, she was diagnosed with Yellow Nail Syndrome. The immunological evaluation was unremarkable overall, with normal T cell subsets and function and adequate antibody titers. Genetic testing identified a heterozygous mutation in the NOD2 gene, c.2107C>T (p.Arg703Cys), considered a variant of uncertain significance. Conclusion: Heterozygous variants in NOD2 can result in a spectrum of autoimmune and autoinflammatory disorders, including Yellow Nail Syndrome. Statement of novelty: We describe a patient with Yellow Nail Syndrome, presenting with the classic triad of clinical features. Genetic evaluation identified a heterozygous variant in NOD2, which has been extensively associated with several autoinflammatory diseases, but not Yellow Nail Syndrome.

Silicon nanowires-based biosensors for the electrical detection of Escherichia coli

One of the main challenges in terms of public health concerns the prevention of bacterial contamination using rapid, highly sensitive and specific detection techniques. The development of highly sensitive bacterial sensors for Escherichia coli detection based on networks of silicon nanowires has been carried out in this work. The interest of these nano-objects takes advantage in a large contact surface allowing potentially important interactions with bacteria. Their presence induces a change in electrical interaction through the silicon nanowires array and is the basis for the development of silicon nanowires based electrical resistances acting as bacteria sensors. High specificity of these sensors is ensured by chemical functionalization of the nanowires allowing the binding of specific antibodies targeting the lipopolysaccharide (anti-LPS) of E. coli, but not S. aureus. The sensor displays a sensitivity of 83 μA per decade of CFU/mL due to the nanometric dimensions of the nanowires. The electrical measurements ensure the detection of various E. coli concentrations down to 102 CFU/mL. This SiNW biosensor device demonstrated its potential as an alternative tool for real-time bacterial detection as miniaturizable and low-cost integrated electronic sensor compatible with the classical silicon technology.

Bacterial hemerythrin domain-containing oxygen and redox sensors: Versatile roles for oxygen and redox signaling.

Hemerythrin is an oxygen-binding protein originally found in certain marine invertebrates. Oxygen reversibly binds at its non-heme diiron center, which consists of two oxo-bridged iron atoms bound to a characteristic conserved set of five His residues, one Glu residue, and one Asp residue. It was recently discovered that several bacteria utilize hemerythrin as an oxygen- and redox-sensing domain in responding to changes in cellular oxygen concentration or redox status, and immediately adapt to these environmental changes in order to maintain important physiological processes, including chemotaxis and c-di-GMP synthesis and degradation. This Mini Review focuses on the recent progress made on structural and functional aspects of these emerging bacterial hemerythrin domain-containing oxygen and redox sensors, revealing characteristic features of this family of proteins.

Characterisation of sequence–structure–function space in sensor–effector integrators of phytochrome-regulated diguanylate cyclases

Understanding the relationship between protein sequence, structure and function is one of the fundamental challenges in biochemistry. A direct correlation, however, is often not trivial since protein dynamics also play an important functional role—especially in signal transduction processes. In a subfamily of bacterial light sensors, phytochrome-activated diguanylate cyclases (PadCs), a characteristic coiled-coil linker element connects photoreceptor and output module, playing an essential role in signal integration. Combining phylogenetic analyses with biochemical characterisations, we were able to show that length and composition of this linker determine sensor–effector function and as such are under considerable evolutionary pressure. The linker length, together with the upstream PHY-specific domain, influences the dynamic range of effector activation and can even cause light-induced enzyme inhibition. We demonstrate phylogenetic clustering according to linker length, and the development of new linker lengths as well as new protein function within linker families. The biochemical characterisation of PadC homologs revealed that the functional coupling of PHY dimer interface and linker element defines signal integration and regulation of output functionality. A small subfamily of PadCs, characterised by a linker length breaking the coiled-coil pattern, shows a markedly different behaviour from other homologs. The effect of the central helical spine on PadC function highlights its essential role in signal integration as well as direct regulation of diguanylate cyclase activity. Appreciation of sensor–effector linkers as integrator elements and their coevolution with sensory modules is a further step towards the use of functionally diverse homologs as building blocks for rationally designed optogenetic tools.Graphical abstract

Rapid and selective electrochemical sensing of bacterial pneumonia in human sputum based on conductive polymer dot electrodes

A rapid wireless electrochemical biosensor that can discriminate between gram-negative and gram-positive bacteria is designed for the selective detection of pneumonia pathogens in human sputum. The selective binding with the bacterial cell wall of gram-negative and gram-positive bacteria is achieved by utilizing colistin- and vancomycin-conjugated polymer dot-coated electrodes (PD-Colis for gram-negative and PD-Vanco for gram-positive, respectively) and can be observed as changes in resistance (ΔR~12–15 kΩ for PD-Colis and ΔR~13–17 kΩ for PD-Vanco). The PD-Colis- and PD-Vanco-coated electrodes demonstrate high sensitivities determined by the low limit of detection (LOD) for both gram-negative (3.0 CFU/mL, R2=0.995) and gram-positive (3.1 CFU/mL, R2=0.994) bacteria. The electrodes can also be used to detect antibiotic-resistant bacteria, such as carbapenem-resistant K. pneumoniae (CRKP) and methicillin-resistant S. aureus (MRSA), as well as enabling selective detection in complex media such as human serum. Moreover, the sensors based on PD-Colis- and PD-Vanco-coated electrodes show excellent performance in real clinical samples such as human sputum. Finally, the integration of the sensor with a wireless sensing system provides in-line bacterial detection and allows monitoring via a smartphone. We anticipate that the bacterial sensor can be potentially used for the rapid and accurate diagnosis of bacterial infections in the clinic.

Exploiting Catabolite Repression and Stringent Response to Control Delay and Multimodality of Bioluminescence Signal by Metal Whole-Cell Biosensors: Interplay between Metal Bioavailability and Nutritional Medium Conditions.

The time-dependent response of metal-detecting whole-cell luminescent bacterial sensors is impacted by metal speciation/bioavailability in solution. The comprehensive understanding of such connections requires the consideration of the bacterial energy metabolism at stake and the effects of supplied food on cells’ capability to convert bioaccumulated metals into light. Accordingly, we investigated the time response (48 h assay) of PzntA-luxCDABE Escherichia coli Cd biosensors in media differing with respect to sources of amino acids (tryptone or Lysogeny Broth) and carbon (glucose, xylose and mixtures thereof). We show that the resulting coupling between the stringent cell response and glucose/xylose-mediated catabolite repressions lead to well-defined multimodalities and shapes of the bioluminescence signal over time. Based on a recent theory for the time–response of metal-sensing luminescent bacteria, successful theoretical reconstructions of the bioluminescence signals are reported under all Cd concentrations (0–20 nM) and nutritive conditions examined. This analysis leads to the evaluation of time-dependent cell photoactivity and qualitative information on metal speciation/bioavailability in solution. Biosensor performance and the position, shape, number, and magnitude of detected peaks are discussed in relation to the metabolic pathways operative during the successive light emission modes identified here over time. Altogether, the results clarify the contributions of metal/nutrient bio-availabilities and food quality to cell response typology.

Differential Detection of Bioavailable Mercury and Cadmium Based on a Robust Dual-Sensing Bacterial Biosensor.

Genetically programmed biosensors have been widely used to monitor bioavailable heavy metal pollutions in terms of their toxicity to living organisms. Most bacterial biosensors were initially designed to detect specific heavy metals such as mercury and cadmium. However, most available biosensors failed to distinguish cadmium from various heavy metals, especially mercury. Integrating diverse sensing elements into a single genetic construct or a single host strain has been demonstrated to quantify several heavy metals simultaneously. In this study, a dual-sensing construct was assembled by employing mercury-responsive regulator (MerR) and cadmium-responsive regulator (CadR) as the separate sensory elements and enhanced fluorescent protein (eGFP) and mCherry red fluorescent protein (mCherry) as the separate reporters. Compared with two corresponding single-sensing bacterial sensors, the dual-sensing bacterial sensor emitted differential double-color fluorescence upon exposure to 0–40 μM toxic Hg(II) and red fluorescence upon exposure to toxic Cd(II) below 200 μM. Bioavailable Hg(II) could be quantitatively determined using double-color fluorescence within a narrow concentration range (0–5 μM). But bioavailable Cd(II) could be quantitatively measured using red fluorescence over a wide concentration range (0–200 μM). The dual-sensing biosensor was applied to detect bioavailable Hg(II) and Cd(II) simultaneously. Significant higher red fluorescence reflected the predominant pollution of Cd(II), and significant higher green fluorescence suggested the predominant pollution of Hg(II). Our findings show that the synergistic application of various sensory modules contributes to an efficient biological device that responds to concurrent heavy metal pollutants in the environment.

Genotyping-by-sequencing-based identification of Arabidopsis pattern recognition receptor RLP32 recognizing proteobacterial translation initiation factor IF1

Activation of plant pattern-triggered immunity (PTI) relies on the recognition of microbe-derived structures, termed patterns, through plant-encoded surface-resident pattern recognition receptors (PRRs). We show that proteobacterial translation initiation factor 1 (IF1) triggers PTI in Arabidopsis thaliana and related Brassicaceae species. Unlike for most other immunogenic patterns, IF1 elicitor activity cannot be assigned to a small peptide epitope, suggesting that tertiary fold features are required for IF1 receptor activation. We have deployed natural variation in IF1 sensitivity to identify Arabidopsis leucine-rich repeat (LRR) receptor-like protein 32 (RLP32) as IF1 receptor using a restriction site-associated DNA sequencing approach. RLP32 confers IF1 sensitivity to rlp32 mutants, IF1-insensitive Arabidopsis accessions and IF1-insensitive Nicotiana benthamiana, binds IF1 specifically and forms complexes with LRR receptor kinases SOBIR1 and BAK1 to mediate signaling. Similar to other PRRs, RLP32 confers resistance to Pseudomonas syringae, highlighting an unexpectedly complex array of bacterial pattern sensors within a single plant species.

Internet of things-based design of maternal and infant monitoring system and adoption of gold nanoparticles bacterial DNA detection technology in probiotic treatment of pregnancy reaction

it aimed to establish a maternal and child monitoring system based on medical Internet of Things (IoT) technology and explore the application of gold magnetic nanoparticles (Au-MNPs) in bacterial detection. The effect of active Bifidobacterium tablet (Siliankang) on intestinal flora of pregnant women and reaction to early pregnancy was analyzed. A real-time fetal heart rate monitoring method was established based on median filtering algorithm, and a maternal and infant monitoring system was established by organically combining portable monitoring equipment and hospital monitoring center through the IoT. Fe3O4 nanoparticles and Au-NPs were prepared by co-precipitation method and Turkevitch-Frens method. Fe3O4-Au-SiO2 NPs was obtained by polymerizing Au-NPs into Fe3O4 nanoparticles and coating the surface with SiO2. The characterization of NPs and its bacterial adsorption efficiency were analyzed, and a capture sensor for the detection of bacterial Deoxyribonucleic acid (DNA) was prepared. A total of 120 patients with pregnancy reaction were selected as the research object, and were divided into the placebo group and the experimental group (compound probiotics supplement group) according to different treatment methods, with 60 patients in each group. The bacterial DNA detection sensor was used to detect the difference of bacterial flora in feces of patients in different groups. The results showed that the particle size of Fe3O4-Au-SiO2 NPs was 15–47 nm, and the adsorption efficiency of Fe3O4-Au-SiO2 NPs to S. aureus, S. epidermidi, E. coli, and P. aeruginosa was higher than 80%. The Fe3O4-Au-SiO2 NPs of the prepared bacterial DNA detection sensor could be hybridized with the target bacterial DNA sequence. the intestinal enterobacteria, enterococci, and Bacteroides of patients in test group were remarkably reduced in contrast to control group, while the Bifidobacterium, Lactobacillus, and Fusobacterium flora were greatly increased (P < 0.05). the number of NVP patients in the control group and test group was 19 case (31.7%) and 5 case (8.3%). The probability of early pregnancy reaction was notably reduced (P < 0.05). It showed that the maternal and infant monitoring system based on Internet of things technology had potential application value for maternal and infant health. Tetralogy of viable Bifidobacterium tablets (Siliankang) can reduce the pathogenic bacteria in the intestines of pregnant women, and then reduced the incidence of early pregnancy reactions.

Rapid printing of a Bacterial array for a Solid-Phase Assay (BacSPA) of heavy metal ions

Bacterial whole-cell biosensors have been used to detect numerous pollutants for decades. In this work, a rapid sensing method using patterned bacterial arrays on solidified agar media was reported. A printing system, which quickly patterns 384-spot bacterial arrays via inertial impact, was developed in this study. The droplet formation was observed by a high-speed camera and simulated in COMSOL software to investigate the printing conditions. We found that the droplet volume and speed were influenced by the accelerations of the impact. Following adjustment, the printer could eject discrete droplets and pattern arrays with high accuracy. The printed bacteria were incubated, and images acquired by a commercial digital camera were analyzed by the Python program. The areas of 384 spots in a single array were similar, with a high roundness and low deviations. We found that the printer plate quality influenced the printing results more than the printing conditions. Finally, the printing system was applied to determine heavy metals concentrations in solid growth media by bioluminescent sensor bacteria. The luminescence intensity patterns varied between heavy metals. We propose the printing system as a useful tool for rapid patterning of bacterial whole cell sensor arrays on solid agar.

Strong Bacterial Cellulose-Based Films with Natural Laminar Alignment for Highly Sensitive Humidity Sensors.

Humidity sensors have been widely used for humidity monitoring in industry and agriculture fields. However, the rigid structure, nondegradability, and large dimension of traditional humidity sensors significantly restrict their applications in wearable fields. In this study, a flexible, strong, and eco-friendly bacterial cellulose-based humidity sensor (BPS) was fabricated using a two-step method, involving solvent evaporation-induced self-assembly and electrolyte permeation. Rapid evaporation of organic solvent induces the formation of nanopores of the bacterial cellulose (BC) surface and promotes structural densification. Furthermore, the successful embedding of potassium hydroxide into the sophisticated network of BC effectively enhanced the sensing performance of BPS. The BPS exhibits an excellent humidity sensing response of more than 103 within the relative humidity ranging from 36.4 to 93% and strong (66.4 MPa) and high flexibility properties owing to the ultrafine fiber network and abundant hydrophilic functional groups of BC. Besides being strong and thin, BPS is also highly flexible, biodegradable, and humidity-sensitive, making it a potential candidate in wearable electronics, human health monitoring, and noncontact switching.

H-NOX proteins in the virulence of pathogenic bacteria.

Nitric oxide (NO) is a toxic gas encountered by bacteria as a product of their own metabolism or as a result of a host immune response. Non-toxic concentrations of NO have been shown to initiate changes in bacterial behaviors such as the transition between planktonic and biofilm-associated lifestyles. The heme nitric oxide/oxygen binding proteins (H-NOX) are a widespread family of bacterial heme-based NO sensors that regulate biofilm formation in response to NO. The presence of H-NOX in several human pathogens combined with the importance of planktonic–biofilm transitions to virulence suggests that H-NOX sensing may be an important virulence factor in these organisms. Here we review the recent data on H-NOX NO signaling pathways with an emphasis on H-NOX homologs from pathogens and commensal organisms. The current state of the field is somewhat ambiguous regarding the role of H-NOX in pathogenesis. However, it is clear that H-NOX regulates biofilm in response to environmental factors and may promote persistence in the environments that serve as reservoirs for these pathogens. Finally, the evidence that large subgroups of H-NOX proteins may sense environmental signals besides NO is discussed within the context of a phylogenetic analysis of this large and diverse family.

The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket

The BarA/UvrY two-component signal transduction system is widely conserved in γ-proteobacteria and provides a link between the metabolic state of the cells and the Csr posttranscriptional regulatory system. In Escherichia coli, the BarA/UvrY system responds to the presence of acetate and other short-chain carboxylic acids by activating transcription of the noncoding RNAs, CsrB and CsrC, which sequester the RNA-binding protein CsrA, a global regulator of gene expression. However, the state of the carboxyl group in the acetate molecule, which serves as the BarA stimulus, and the signal reception site of BarA remain unknown. In this study, we show that the deletion or replacement of the periplasmic domain of BarA and also the substitution of certain hydroxylated and hydrophobic amino acid residues in this region, result in a sensor kinase that remains unresponsive to its physiological stimulus, demonstrating that the periplasmic region of BarA constitutes a functional detector domain. Moreover, we provide evidence that the protonated state of acetate or formate serves as the physiological stimulus of BarA. In addition, modeling of the BarA sensor domain and prediction of the signal-binding site, by blind molecular docking, revealed a calcium channels and chemotaxis receptors domain with a conserved binding pocket, which comprised uncharged polar and hydrophobic amino acid residues. Based on the comparative sequence and phylogenetic analyses, we propose that, at least, two types of BarA orthologues diverged and evolved separately to acquire distinct signal-binding properties, illustrating the wide adaptability of the bacterial sensor kinase proteins.

Coevolution of the bacterial pheromone ComS and sensor ComR fine-tunes natural transformation in streptococci

Competence for natural transformation extensively contributes to genome evolution and the rapid adaptability of bacteria dwelling in challenging environments. In most streptococci, this process is tightly controlled by the ComRS signaling system, which is activated through the direct interaction between the (R)RNPP-type ComR sensor and XIP pheromone (mature ComS). The overall mechanism of activation and the basis of pheromone selectivity have been previously reported in Gram-positive salivarius streptococci; however, detailed 3D-remodeling of ComR leading up to its activation remains only partially understood. Here, we identified using a semirational mutagenesis approach two residues in the pheromone XIP that bolster ComR sensor activation by interacting with two aromatic residues of its XIP-binding pocket. Random and targeted mutagenesis of ComR revealed that the interplay between these four residues remodels a network of aromatic–aromatic interactions involved in relaxing the sequestration of the DNA-binding domain. Based on these data, we propose a comprehensive model for ComR activation based on two major conformational changes of the XIP-binding domain. Notably, the stimulation of this newly identified trigger point by a single XIP substitution resulted in higher competence and enhanced transformability, suggesting that pheromone-sensor coevolution counter-selects for hyperactive systems in order to maintain a trade-off between competence and bacterial fitness. Overall, this study sheds new light on the ComRS activation mechanism and how it could be exploited for biotechnological and biomedical purposes.

Diversity in Sensing and Signaling of Bacterial Sensor Histidine Kinases

Two-component signal transduction systems (TCSs) are widely conserved in bacteria to respond to and adapt to the changing environment. Since TCSs are also involved in controlling the expression of virulence, biofilm formation, quorum sensing, and antimicrobial resistance in pathogens, they serve as candidates for novel drug targets. TCSs consist of a sensor histidine kinase (HK) and its cognate response regulator (RR). Upon perception of a signal, HKs autophosphorylate their conserved histidine residues, followed by phosphotransfer to their partner RRs. The phosphorylated RRs mostly function as transcriptional regulators and control the expression of genes necessary for stress response. HKs sense their specific signals not only in their extracytoplasmic sensor domain but also in their cytoplasmic and transmembrane domains. The signals are sensed either directly or indirectly via cofactors and accessory proteins. Accumulating evidence shows that a single HK can sense and respond to multiple signals in different domains. The underlying molecular mechanisms of how HK activity is controlled by these signals have been extensively studied both biochemically and structurally. In this article, we introduce the wide diversity of signal perception in different domains of HKs, together with their recently clarified structures and molecular mechanisms.