signal transduction systems
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2022 ◽  
Author(s):  
Pengchao Wang ◽  
Guangming Zhang ◽  
Zeling Xu ◽  
Zhe Chen ◽  
Xiaohong Liu ◽  
...  

Bacteria adapt to the constantly changing environments largely by transcriptional regulation through the activities of various transcription factors (TFs). However, techniques that monitor the in situ TF-promoter interactions in living bacteria are lacking. Herein, we developed a whole-cell TF-promoter binding assay based on the intermolecular Förster resonance energy transfer (FRET) between a fluorescent unnatural amino acid CouA which is genetically encoded into defined sites in TFs and the live cell fluorescent nucleic acid stain SYTO 9. We show that this new FRET pair monitors the intricate TF-promoter interactions elicited by various types of signal transduction systems with specificity and sensitivity. Furthermore, the assay is applicable to identify novel modulators of the regulatory systems of interest and monitor TF activities in bacteria colonized in C. elegans. In conclusion, we established a tractable and sensitive TF-promoter binding assay in living bacteria which not only complements currently available approaches for DNA-protein interactions but also provides novel opportunities for functional annotation of bacterial signal transduction systems and studies of the bacteria-host interface.


2022 ◽  
Vol 12 ◽  
Author(s):  
Ruojun Wang ◽  
Weipeng Zhang ◽  
Wei Ding ◽  
Zhicong Liang ◽  
Lexin Long ◽  
...  

Microbes use signal transduction systems in the processes of swarming motility, antibiotic resistance, virulence, conjugal plasmid transfer, and biofilm formation. However, the signal transduction systems in natural marine biofilms have hardly been profiled. Here we analyzed signal transduction genes in 101 marine biofilm and 91 seawater microbial metagenomes. The abundance of almost all signal transduction-related genes in biofilm microbial communities was significantly higher than that in seawater microbial communities, regardless of substrate types, locations, and durations for biofilm development. In addition, the dominant source microbes of signal transduction genes in marine biofilms were different from those in seawater samples. Co-occurrence network analysis on signal communication between microbes in marine biofilms and seawater microbial communities revealed potential inter-phyla interactions between microorganisms from marine biofilms and seawater. Moreover, phylogenetic tree construction and protein identity comparison displayed that proteins related to signal transductions from Red Sea biofilms were highly similar to those from Red Sea seawater microbial communities, revealing a possible biological basis of interspecies interactions between surface-associated and free-living microbial communities in a local marine environment. Our study revealed the special profile and enrichment of signal transduction systems in marine biofilms and suggested that marine biofilms participate in intercellular interactions of the local ecosystem where they were seeded.


mBio ◽  
2021 ◽  
Author(s):  
Mingshan Li ◽  
Xianjin Xu ◽  
Xiaoqin Zou ◽  
Gerald L. Hazelbauer

Two-component signal transduction systems are a primary means by which bacteria sense and respond to their environment. Response regulators are key components of these systems.


Author(s):  
Chelsea L. Murphy ◽  
R. Yang ◽  
T. Decker ◽  
C. Cavalliere ◽  
V. Andreev ◽  
...  

Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, non-soil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring (Zodletone spring) in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes, and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of thirteen distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g. FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine-learning approaches based on a set of 634 genes informative of social lifestyle predicted a non-social behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities, but encoded genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 Mya in response to the rise of soil as a distinct habitat on earth. Importance The Myxococcota is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured Myxococcota are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the Myxococcota have been encountered in a wide range of non-soil, predominantly anaerobic habitats; and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remain unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA that represent novel, yet-uncultured, orders and families in the Myxococcota. The genomes appear to lack the characteristic hallmarks for social behavior encountered in Myxococcota genomes, and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity was confirmed through detailed comparative genomic analysis of thirteen pathways associated with Myxococcota social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel Myxococcota are predicted to be strict anaerobes, utilizing fermentation, nitrate reduction, and dissimilarity sulfate reduction for energy acquisition. Our results highlight the broad patterns of metabolic diversity within the yet-uncultured Myxococcota and suggest that the evolution of predation and fruiting body formation in the Myxococcota has occurred in response to soil formation as a distinct habitat on earth.


2021 ◽  
Author(s):  
Collin Kessler ◽  
Eisha Mhatre ◽  
Vaughn S Cooper ◽  
Wook Kim

Bacteria rapidly adapt to their environment by integrating external stimuli through diverse signal transduction systems. Pseudomonas aeruginosa, for example, senses surface-contact through the Wsp signal transduction system to trigger the production of cyclic di-GMP. Diverse mutations in wsp genes that manifest enhanced biofilm formation are frequently reported in clinical isolates of P. aeruginosa, and in biofilm studies of Pseudomonas spp. and Burkholderia cenocepacia. In contrast to the convergent phenotypes associated with comparable wsp mutations, we demonstrate that the Wsp system in B. cenocepacia does not impact intracellular cyclic di-GMP levels unlike that in Pseudomonas spp. Our current mechanistic understanding of the Wsp system is entirely based on the study of four Pseudomonas spp. and its phylogenetic distribution remains unknown. Here, we present the first broad phylogenetic analysis to date to show that the Wsp system originated in the β-proteobacteria then horizontally transferred to Pseudomonas spp., the sole member of the γ-proteobacteria. Alignment of 794 independent Wsp systems with reported mutations from the literature identified key amino acid residues that fall within and outside annotated functional domains. Specific residues that are highly conserved but uniquely modified in B. cenocepacia likely define mechanistic differences among Wsp systems. We also find the greatest sequence variation in the extracellular sensory domain of WspA, indicating potential adaptations to diverse external stimuli beyond surface-contact sensing. This study emphasizes the need to better understand the breadth of functional diversity of the Wsp system as a major regulator of bacterial adaptation beyond B. cenocepacia and select Pseudomonas spp.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jennifer M Kunselman ◽  
Achla Gupta ◽  
Ivone gomes ◽  
Lakshmi A Devi ◽  
Manojkumar A Puthenveedu

Many signal transduction systems have an apparent redundancy built into them, where multiple physiological agonists activate the same receptors. Whether this is true redundancy, or whether this provides an as-yet unrecognized specificity in downstream signaling, is not well understood. We address this question using the kappa opioid receptor (KOR), a physiologically relevant G protein-coupled receptor (GPCR) that is activated by multiple members of the Dynorphin family of opioid peptides. We show that two related peptides, Dynorphin A and Dynorphin B, bind and activate KOR to similar extents in mammalian neuroendocrine cells and rat striatal neurons, but localize KOR to distinct intracellular compartments and drive different post-endocytic fates of the receptor. Strikingly, localization of KOR to the degradative pathway by Dynorphin A induces sustained KOR signaling from these compartments. Our results suggest that seemingly redundant endogenous peptides can fine-tune signaling by regulating the spatiotemporal profile of KOR signaling.


mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Dehong Zheng ◽  
Huihui Wang ◽  
Hao Zhong ◽  
Wenli Ke ◽  
Huifeng Hu ◽  
...  

ABSTRACT Xanthomonas is a notorious plant pathogen causing serious diseases in hundreds of plant hosts. Xanthomonas species are equipped with an array of signal transduction systems that regulate gene expression to survive in various harsh environments and successfully infect hosts. Although certain pathogenicity-associated regulators have been functionally characterized, signal transduction systems always function as a regulatory network which remains to be elucidated in Xanthomonas. This study used a systematic approach to characterize all identified pathogenicity-associated regulators in Xanthomonas oryzae pv. oryzae (Xoo), including a transcriptional regulator with unknown function, and their interactive regulatory network. RNA sequencing was used in elucidating the patterns of the 10 pathogenicity-associated regulators identified. Results revealed that each pathogenicity-associated regulator has cross talk with others and all these regulators function as a regulatory network, with VemR and PXO_RS20790 being the master pathogenicity-associated regulators and HrpX being the final executant. Moreover, regulome analysis showed that numerous genes other than genes in pathogenicity islands are finely regulated within the regulatory network. Given that most of the pathogenicity-associated regulators are conserved in Xanthomonadales, our findings suggest a global network of gene regulation in this evolutionarily conserved pathogen. In conclusion, our study provides essential basic information about the regulatory network in Xoo, suggesting that this complicated regulatory network is one of the reasons for the robustness and fitness of Xanthomonas spp. IMPORTANCE The host plant infection process of pathogenic bacteria is a coordinating cellular behavior, which requires dynamic regulation at several levels in response to variations in host plants or fluctuations in the external environment. As one of the most important genera of plant-pathogenic bacteria, Xanthomonas has been studied as a model. Although certain pathogenicity-associated regulators have been functionally characterized, interactions among them remain to be elucidated. This study systematically characterized pathogenicity-associated regulators in Xoo and revealed that cross talk exists among pathogenicity-associated regulators and function as a regulatory network in which a hierarchy exists among the regulators. Our study elucidated the landscape of the pathogenicity-associated regulatory network in Xanthomonas, promoting understanding of the infection process of pathogenic bacteria.


2021 ◽  
Vol 11 ◽  
Author(s):  
P. Boknik ◽  
J. Eskandar ◽  
B. Hofmann ◽  
N. Zimmermann ◽  
J. Neumann ◽  
...  

This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A2A-AR in cells in the living heart, as well as the known interactions of A2A-AR with membrane-bound receptors, will be addressed. The possible role that the receptors play in some relevant cardiac pathologies, such as persistent or transient ischemia, hypoxia, sepsis, hypertension, cardiac hypertrophy, and arrhythmias, will be reviewed. Moreover, the cardiac utility of A2A-AR as therapeutic targets for agonistic and antagonistic drugs will be discussed. Gaps in our knowledge about the cardiac function of A2A-AR and future research needs will be identified and formulated.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arumugam Priya ◽  
Chandra Bose Manish Kumar ◽  
Alaguvel Valliammai ◽  
Anthonymuthu Selvaraj ◽  
Shunmugiah Karutha Pandian

AbstractThe principal etiological agent of human dental caries, Streptococcus mutans is a multi-virulent pathogen that can transform commensal oral microbial community to plaque biofilms. Major virulence factors that are associated with the cariogenicity of S. mutans include adhesion, acidogenicity and acidurity. All these pathogenic traits coordinate and alter the dental plaque ecology which provide room for interaction with other similar acidogenic and aciduric bacteria. This cariogenic flora increases the possibility of enamel demineralization which headway to caries development. The present study was aimed at evaluating the antimicrobial and antiinfective potential of a lichen secondary metabolite usnic acid (UA) against S. mutans. Minimum inhibitory concentration (MIC), Minimum bactericidal concentration (MBC) and growth kinetics were evaluated to determine the antimicrobial potential of UA against S. mutans. UA at 5 µg mL−1 and 10 µg mL−1 concentration were considered as MIC and MBC respectively. Effect on biofilm formation was microscopically assessed and found to be reduced in a concentration dependent manner. Gene expression of gtfB, gtfC, gtfD, vicR, ComDE and smu0630 was found to be downregulated upon treatment with sub-MIC of UA. Acidogenicity, acidurity, eDNA synthesis and response to oxidative stress were found to be attenuated by the influence of UA. It was also demonstrated to act on preformed mature biofilm of S. mutans. Moreover, UA was shown to possess very low frequency to acquire spontaneous resistance development in S. mutans. Besides, no morphological aberrations or toxic effect was instigated by UA in the human buccal epithelial cells as well as to the oral commensals. Altogether, these results demonstrate the therapeutic potential of usnic acid in the treatment of S. mutans infection.


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