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https://www.readbyqxmd.com/read/29311281/cyclic-di-gmp-regulates-tfoy-in-vibrio-cholerae-to-control-motility-by-both-transcriptional-and-posttranscriptional-mechanisms
#1
Benjamin R Pursley, Michael M Maiden, Meng-Lun Hsieh, Nicolas Fernandez, Geoffrey B Severin, Christopher M Waters
Cyclic di-GMP (c-di-GMP) is a bacterial second messenger molecule that is a key global regulator in Vibrio cholerae, but the molecular mechanisms by which this molecule regulates downstream phenotypes have not been fully characterized. One such regulatory factor that may respond to c-di-GMP is the Vc2 c-di-GMP-binding riboswitch that is hypothesized to control the expression of the downstream putative transcription factor TfoY. Although much is known about the physical and structural properties of the Vc2 riboswitch aptamer, the nature of its expression and function in V...
January 8, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29247853/cytosolic-sensing-of-immuno-stimulatory-dna-the-enemy-within
#2
REVIEW
Rekha Dhanwani, Mariko Takahashi, Sonia Sharma
In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I)...
December 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29213262/the-oxidative-stress-agent-hypochlorite-stimulates-c-di-gmp-synthesis-and-biofilm-formation-in-pseudomonas-aeruginosa
#3
Nikola Strempel, Michael Nusser, Anke Neidig, Gerald Brenner-Weiss, Joerg Overhage
The opportunistic human pathogen Pseudomonas aeruginosa is able to survive under a variety of often harmful environmental conditions due to a multitude of intrinsic and adaptive resistance mechanisms, including biofilm formation as one important survival strategy. Here, we investigated the adaptation of P. aeruginosa PAO1 to hypochlorite (HClO), a phagocyte-derived host defense compound and frequently used disinfectant. In static biofilm assays, we observed a significant enhancement in initial cell attachment in the presence of sublethal HClO concentrations...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29203646/structural-and-biochemical-characterization-of-the-catalytic-domains-of-gdpp-reveals-a-unified-hydrolysis-mechanism-for-the-dhh-dhha1-phosphodiesterase
#4
Feng Wang, Qing He, Kaixuan Su, Tiandi Wei, Sujuan Xu, Lichuan Gu
The Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterases (PDEs) that catalyze degradation of cyclic di-adenosine monophosphate (c-di-AMP) could be subdivided into two subfamilies based on the final product is 5'-phosphadenylyl-adenosine (5'-pApA) or AMP. In previous study we revealed that Rv2837c, a stand-alone DHH/DHHA1 PDE, employs a 5'-pApA internal flipping mechanism to produce AMPs. However, why the membrane-bound DHH/DHHA1 PDE can only degrade c-di-AMP to 5'-pApA remains obscure...
December 4, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29158434/high-levels-of-cyclic-di-gmp-in-klebsiella-pneumoniae-attenuate-virulence-in-the-lung
#5
David A Rosen, Joy Twentyman, David A Hunstad
The bacterial second messenger, bis-(3' -5')-cyclic dimeric guanosine monophosphate (c-di-GMP) has been shown to influence expression of virulence factors in certain pathogenic bacteria, but little is known about its activity in the increasingly antibiotic-resistant pathogen Klebsiella pneumoniae Here, expression in K. pneumoniae of a heterologous diguanylate cyclase increased bacterial c-di-GMP concentration and attenuated pathogenesis in murine pneumonia. This attenuation remained evident in mice lacking the c-di-GMP sensor STING, indicating that high c-di-GMP exerted its influence not on host responses, but on bacterial physiology...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158389/burkholderia-cenocepacia-integrates-cis-2-dodecenoic-acid-and-cyclic-dimeric-guanosine-monophosphate-signals-to-control-virulence
#6
Chunxi Yang, Chaoyu Cui, Qiumian Ye, Jinhong Kan, Shuna Fu, Shihao Song, Yutong Huang, Fei He, Lian-Hui Zhang, Yantao Jia, Yong-Gui Gao, Caroline S Harwood, Yinyue Deng
Quorum sensing (QS) signals are used by bacteria to regulate biological functions in response to cell population densities. Cyclic diguanosine monophosphate (c-di-GMP) regulates cell functions in response to diverse environmental chemical and physical signals that bacteria perceive. In Burkholderia cenocepacia, the QS signal receptor RpfR degrades intracellular c-di-GMP when it senses the QS signal cis-2-dodecenoic acid, also called Burkholderia diffusible signal factor (BDSF), as a proxy for high cell density...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29146598/structural-analyses-unravel-the-molecular-mechanism-of-cyclic-di-gmp-regulation-of-bacterial-chemotaxis-via-a-pilz-adaptor-protein
#7
Xin-Fu Yan, Lingyi Xin, Jackie Tan Yen, Yukai Zeng, Shengyang Jin, Qing Wei Cheang, Rachel Andrea Chea Yuen Fong, Keng-Hwee Chiam, Zhao-Xun Liang, Yong-Gui Gao
The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility and pathogenicity. Cdi-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism in c-di-GMP-mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ co-crystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa This co-crystal structure, together with the structure of free CheR1, revealed that the binding of c-di-GMP induces dramatic structural changes in MapZ that are crucial for CheR1 binding...
November 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29091392/thiol-benzo-triazolo-quinazolinone-covalently-modifies-alg44-to-inhibit-c-di-gmp-binding-and-reduces-alginate-production-by-pseudomonas-aeruginosa
#8
Eric Zhou, Anna B Seminara, Soo-Kyoung Kim, Cherisse L Hall, Yan Wang, Vincent T Lee
Pseudomonas aeruginosa is an opportunistic pathogen that affects a large proportion of cystic fibrosis (CF) patients. CF patients have dehydrated mucus within the airways that leads to the inability of the mucociliary escalator to expel inhaled microbes. Once inhaled, P. aeruginosa can persist in the lungs of the CF patients for the remainder of their lives. During this chronic infection, a phenomenon called mucoid conversion can occur in which P. aeruginosa can mutate and inactivate their mucA gene. As a consequence, transcription of the alg operon is highly expressed leading to the copious secretion of the alginate exopolysaccharide, which is associated with decreased lung function and increased CF patient morbidity and mortality...
November 1, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29091032/cyclic-di-gmp-differentially-tunes-a-bacterial-flagellar-motor-through-a-novel-class-of-chey-like-regulators
#9
Jutta Nesper, Isabelle Hug, Setsu Kato, Chee-Seng Hee, Judith Maria Habazettl, Pablo Manfredi, Stephan Grzesiek, Tilman Schirmer, Thierry Emonet, Urs Jenal
The flagellar motor is a sophisticated rotary machine facilitating locomotion and signal transduction. Owing to its important role in bacterial behavior, its assembly and activity are tightly regulated. For example, chemotaxis relies on a sensory pathway coupling chemical information to rotational bias of the motor through phosphorylation of the motor switch protein CheY. Using a chemical proteomics approach, we identified a novel family of CheY-like (Cle) proteins in Caulobacter crescentus, which tune flagellar activity in response to binding of the second messenger c-di-GMP to a C-terminal extension...
November 1, 2017: ELife
https://www.readbyqxmd.com/read/29090193/reduced-intracellular-c-di-gmp-content-increases-expression-of-quorum-sensing-regulated-genes-in-pseudomonas-aeruginosa
#10
Song Lin Chua, Yang Liu, Yingying Li, Hui Jun Ting, Gurjeet S Kohli, Zhao Cai, Pipob Suwanchaikasem, Kelvin Kau Kit Goh, Sean Pin Ng, Tim Tolker-Nielsen, Liang Yang, Michael Givskov
Cyclic-di-GMP (c-di-GMP) is an intracellular secondary messenger which controls the biofilm life cycle in many bacterial species. High intracellular c-di-GMP content enhances biofilm formation via the reduction of motility and production of biofilm matrix, while low c-di-GMP content in biofilm cells leads to increased motility and biofilm dispersal. While the effect of high c-di-GMP levels on bacterial lifestyles is well studied, the physiology of cells at low c-di-GMP levels remains unclear. Here, we showed that Pseudomonas aeruginosa cells with high and low intracellular c-di-GMP contents possessed distinct transcriptome profiles...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29072834/light-regulated-synthesis-of-cyclic-di-gmp-by-a-bidomain-construct-of-the-cyanobacteriochrome-tlr0924-sesa-without-stable-dimerization
#11
Matthew Blain-Hartung, Nathan C Rockwell, J Clark Lagarias
Phytochromes and cyanobacteriochromes (CBCRs) use double-bond photoisomerization of their linear tetrapyrrole (bilin) chromophores within cGMP-specific phosphodiesterases/adenylyl cyclases/FhlA (GAF) domain-containing photosensory modules to regulate activity of C-terminal output domains. CBCRs exhibit photocycles that are much more diverse than those of phytochromes and are often found in large modular proteins such as Tlr0924 (SesA), one of three blue light regulators of cell aggregation in the cyanobacterium Thermosynechococcus elongatus...
November 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/29068284/the-agrobacterium-tumefaciens-chey-like-protein-clar-regulates-biofilm-formation
#12
Nathan Feirer, DohHyun Kim, Jing Xu, Nico Fernandez, Christopher M Waters, Clay Fuqua
The switch from a motile, planktonic existence to an attached biofilm is a major bacterial lifestyle transition that is often mediated by complex regulatory pathways. In this report, we describe a CheY-like protein required for control of the motile-to-sessile switch in the plant pathogen Agrobacterium tumefaciens. This regulator, which we have designated ClaR, possesses two distinct CheY-like receiver (REC) domains and is involved in the negative regulation of biofilm formation, through production of the unipolar polysaccharide (UPP) adhesin and cellulose...
October 25, 2017: Microbiology
https://www.readbyqxmd.com/read/29063141/cmpx-affects-virulence-in-pseudomonas-aeruginosa-through-the-gac-rsm-signaling-pathway-and-by-modulating-c-di-gmp-levels
#13
Anjali Y Bhagirath, Deepti Somayajula, Yanqi Li, Kangmin Duan
Pseudomonas aeruginosa is an ubiquitous organism which is able to infect and colonize many types of hosts including humans. Colonization of P. aeruginosa in chronic infections leads to the formation of biofilms, which are difficult to eradicate. P. aeruginosa is capable of regulating its virulence factors in response to external environment triggers and its signaling mechanism involves two-component regulatory systems and small molecules such as bis-(3'-5')-cyclic dimeric guanosine monophosphate. PA1611-RetS-GacS/A-RsmA/Y/Z is a key regulatory pathway in P...
October 23, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29056046/synthesis-of-all-possible-canonical-3-5-linked-cyclic-dinucleotides-and-evaluation-of-riboswitch-interactions-and-immune-stimulatory-effects
#14
Changhao Wang, Malte Sinn, Julia Stifel, Anna C Heiler, Annette Sommershof, Jörg S Hartig
The cyclic dinucleotides (CDNs) c-di-GMP, c-di-AMP, and c-AMP-GMP are widely utilized as second messengers in bacteria, where they signal lifestyle changes such as motility and biofilm formation, cell wall and membrane homeostasis, virulence, and exo-electrogenesis. For all known bacterial CDNs, specific riboswitches have been identified that alter gene expression in response to the second messengers. In addition, bacterial CDNs trigger potent immune responses, making them attractive as adjuvants in immune therapies...
November 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29052983/in-vivo-biochemistry-single-cell-dynamics-of-cyclic-di-gmp-in-e-coli-in-response-to-zinc-overload
#15
Jongchan Yeo, Andrew B Dippel, Xin C Wang, Ming C Hammond
Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities in vivo remain highly challenging to study in real-time and for individual cells. Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP...
October 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/29038053/flagellar-motility-extracellular-proteases-and-vibrio-cholerae-detachment-from-abiotic-and-biotic-surfaces
#16
Loree Mewborn, Jorge A Benitez, Anisia J Silva
Vibrio cholerae of serogroups O1 and O139, the causative agent of Asiatic cholera, continues to be a major global health threat. This pathogen utilizes substratum-specific pili to attach to distinct surfaces in the aquatic environment and the human small intestine and detaches when conditions become unfavorable. Both attachment and detachment are critical to bacterial environmental survival, pathogenesis and disease transmission. However, the factors that promote detachment are less understood. In this study, we examine the role of flagellar motility and hemagglutinin/protease (HapA) in vibrio detachment from a non-degradable abiotic surface and from the suckling mouse intestine...
October 13, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29034850/pseudomonas-aeruginosa-variants-obtained-from-veterinary-clinical-samples-reveal-a-role-for-cyclic-di-gmp-in-biofilm-formation-and-colony-morphology
#17
Maria T Brock, Galya C Fedderly, Grace I Borlee, Michael M Russell, Liliana K Filipowska, Doreene R Hyatt, Ryan A Ferris, Bradley R Borlee
Overuse of antibiotics is contributing to an emerging antimicrobial resistance crisis. To better understand how bacteria adapt tolerance and resist antibiotic treatment, Pseudomonas aeruginosa isolates obtained from infection sites sampled from companion animals were collected and evaluated for phenotypic differences. Selected pairs of clonal isolates were obtained from individual infection samples and were assessed for antibiotic susceptibility, cyclic di-GMP levels, biofilm production, motility and genetic-relatedness...
October 16, 2017: Microbiology
https://www.readbyqxmd.com/read/29018125/more-than-enzymes-that-make-or-break-cyclic-di-gmp-local-signaling-in-the-interactome-of-ggdef-eal-domain-proteins-of-escherichia-coli
#18
Olga Sarenko, Gisela Klauck, Franziska M Wilke, Vanessa Pfiffer, Anja M Richter, Susanne Herbst, Volkhard Kaever, Regine Hengge
The bacterial second messenger bis-(3'-5')-cyclic diguanosine monophosphate (c-di-GMP) ubiquitously promotes bacterial biofilm formation. Intracellular pools of c-di-GMP seem to be dynamically negotiated by diguanylate cyclases (DGCs, with GGDEF domains) and specific phosphodiesterases (PDEs, with EAL or HD-GYP domains). Most bacterial species possess multiple DGCs and PDEs, often with surprisingly distinct and specific output functions. One explanation for such specificity is "local" c-di-GMP signaling, which is believed to involve direct interactions between specific DGC/PDE pairs and c-di-GMP-binding effector/target systems...
October 10, 2017: MBio
https://www.readbyqxmd.com/read/28990312/cyclic-di-gmp-regulation-of-virulence-in-bacterial-pathogens
#19
REVIEW
Cherisse L Hall, Vincent T Lee
Signaling pathways allow bacteria to adapt to changing environments. For pathogenic bacteria, signaling pathways allow for timely expression of virulence factors and the repression of antivirulence factors within the mammalian host. As the bacteria exit the mammalian host, signaling pathways enable the expression of factors promoting survival in the environment and/or nonmammalian hosts. One such signaling pathway uses the dinucleotide cyclic-di-GMP (c-di-GMP), and many bacterial genomes encode numerous proteins that are responsible for synthesizing and degrading c-di-GMP...
October 8, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28970274/a-model-of-equine-endometritis-involving-a-pseudomonas-aeruginosa-biofilm
#20
Ryan A Ferris, Patrick M McCue, Grace I Borlee, Kristina E Glapa, Kevin H Martin, Mihnea R Mangalea, Margo L Hennet, Lisa M Wolfe, Corey D Broeckling, Bradley R Borlee
Bacteria in a biofilm community have increased tolerance to antimicrobial therapy. To characterize the role of biofilms in equine endometritis, six mares were inoculated with lux-engineered Pseudomonas aeruginosa strains isolated from equine uterine infections. Following establishment of infection, the horses were euthanized and the endometrial surfaces were imaged for luminescence to localize adherent lux-labeled bacteria. Samples from the endometrium were collected for cytology, histopathology, carbohydrate analysis, and expression of inflammatory cytokine genes...
October 2, 2017: Infection and Immunity
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