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https://www.readbyqxmd.com/read/28333574/cytosolic-nucleic-acid-sensors-and-innate-immune-regulation
#1
Daisuke Ori, Motoya Murase, Taro Kawai
During viral and bacterial infections, pathogen-derived cytosolic nucleic acids are recognized by the intracellular RNA sensors retinoic acid-inducible gene I and melanoma-differentiated gene 5 and intracellular DNA sensors, including cyclic-di-GMP-AMP synthase, absent in melanoma 2, interferon (IFN)-gamma inducible protein 16, polymerase III, and so on. Binding of intracellular nucleic acids to these sensors activates downstream signaling cascades, resulting in the production of type I IFNs and pro-inflammatory cytokines to induce appropriate systematic immune responses...
March 23, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28328921/versatile-modes-of-cellular-regulation-via-cyclic-dinucleotides
#2
REVIEW
Petya Violinova Krasteva, Holger Sondermann
Since the discovery of c-di-GMP almost three decades ago, cyclic dinucleotides (CDNs) have emerged as widely used signaling molecules in most kingdoms of life. The family of second messengers now includes c-di-AMP and distinct versions of mixed cyclic GMP-AMP (cGAMP) compounds. In addition to these nucleotides, a vast number of proteins for the production and turnover of these molecules have been described, as well as effectors that translate the signals into physiological responses. The latter include, but are not limited to, mechanisms for adaptation and survival in prokaryotes, persistence and virulence of bacterial pathogens, and immune responses to viral and bacterial invasion in eukaryotes...
March 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28296273/cyclic-di-gmp-signaling-meets-extracellular-polysaccharide-synthesis-in-bacillus-subtilis
#3
Jan Kampf, Jörg Stülke
In order to resist harmful environmental conditions, many bacteria form multicellular aggregates called biofilms. In these biofilms, they protect themselves in a self-produced matrix consisting of extracellular polysaccharides, proteins, and DNA. In many bacteria, biofilm formation is stimulated in the presence of the second messenger cyclic di-GMP. In this issue of Environmental Microbiology Reports, Bedrunka and Graumann have studied matrix production by the proteins encoded in the Bacillus subtilis ydaJKLMN operon...
March 13, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28263305/cyclic-di-gmp-regulates-lipopolysaccharide-modification-and-contributes-to-pseudomonas-aeruginosa-immune-evasion
#4
Ronan R McCarthy, Maria J Mazon-Moya, Joana A Moscoso, Youai Hao, Joseph S Lam, Christophe Bordi, Serge Mostowy, Alain Filloux
Pseudomonas aeruginosa is a Gram-negative bacterial pathogen associated with acute and chronic infections. The universal cyclic-di-GMP second messenger is instrumental in the switch from a motile lifestyle to resilient biofilm as in the cystic fibrosis lung. The SadC diguanylate cyclase is associated with this patho-adaptive transition. Here, we identify an unrecognized SadC partner, WarA, which we show is a methyltransferase in complex with a putative kinase, WarB. We established that WarA binds to cyclic-di-GMP, which potentiates its methyltransferase activity...
March 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28259672/the-staphylococcus-epidermidis-gdps-regulates-biofilm-formation-independently-of-its-protein-coding-function
#5
Tao Zhu, Yanfeng Zhao, Yang Wu, Di Qu
The second messenger cyclic di-guanylate (c-di-GMP) plays an important role in controlling the switch between planktonic and biofilm lifestyles. The synthesis of c-di-GMP is catalyzed by di-guanylate cyclases (DGCs) and the enzymes are characterized by the presence of a conserved GGDEF domain. In the sequenced staphylococcal genomes, gdpS is the only gene encoding a GGDEF domain-containing protein. Previous studies have shown that gdpS contributes to staphylococcal biofilm formation, but its effect remains under debate...
March 1, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28243692/intratumoral-administration-of-cgamp-transiently-accumulates-potent-macrophages-for-anti-tumor-immunity-at-a-mouse-tumor-site
#6
Takayuki Ohkuri, Akemi Kosaka, Kei Ishibashi, Takumi Kumai, Yui Hirata, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi
Stimulator of IFN genes (STING) spontaneously contributes to anti-tumor immunity by inducing type I interferons (IFNs) following sensing of tumor-derived genomic DNAs in the tumor-bearing host. Although direct injection of STING ligands such as cyclic diguanylate monophosphate (c-di-GMP) and cyclic [G(2',5')pA(3',5')p] (cGAMP) into the tumor microenvironment exerts anti-tumor effects through strong induction of type I IFNs and activation of innate and adaptive immunity, the precise events caused by STING in the tumor microenvironment remain to be elucidated...
February 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28242722/cyclic-di-gmp-binding-by-an-assembly-atpase-pilb2-and-control-of-type-iv-pilin-polymerization-in-the-gram-positive-pathogen-clostridium-perfringens
#7
William A Hendrick, Mona W Orr, Samantha R Murray, Vincent T Lee, Stephen B Melville
The Gram-positive pathogen Clostridium perfringens possesses Type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in C. perfringens, called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1-PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the pilB2 and pilC2 genes...
February 27, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28186120/dimerisation-induced-formation-of-the-active-site-and-the-identification-of-three-metal-sites-in-eal-phosphodiesterases
#8
Dom Bellini, Sam Horrell, Andrew Hutchin, Curtis W Phippen, Richard W Strange, Yuming Cai, Armin Wagner, Jeremy S Webb, Ivo Tews, Martin A Walsh
The bacterial second messenger cyclic di-3',5'-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the Pseudomonas aeruginosa proteins PA3825 (PA3825(EAL)) and PA1727 (MucR(EAL))...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28171809/the-ins-and-outs-of-cyclic-di-gmp-signaling-in-vibrio-cholerae
#9
REVIEW
Jenna G Conner, David Zamorano-Sánchez, Jin Hwan Park, Holger Sondermann, Fitnat H Yildiz
The second messenger nucleotide cyclic dimeric guanosine monophosphate (c-di-GMP) governs many cellular processes in the facultative human pathogen Vibrio cholerae. This organism copes with changing environmental conditions in aquatic environments and during transitions to and from human hosts. Modulation of c-di-GMP allows V. cholerae to shift between motile and sessile stages of life, thus allowing adaptation to stressors and environmental conditions during its transmission cycle. The V. cholerae genome encodes a large set of proteins predicted to degrade and produce c-di-GMP...
February 4, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28167523/the-role-of-cyclic-di-gmp-and-exopolysaccharide-in-type-iv-pilus-dynamics
#10
Jan Ribbe, Amy E Baker, Sebstian Euler, George A O'Toole, Berenike Maier
For Pseudomonas aeruginosa the levels of cyclic di-GMP govern the transition from the planktonic state to biofilm formation. Type IV pili (T4P) are crucial determinants of biofilm structure and dynamics, but it is unknown how the levels of c-di-GMP affect pilus dynamics. Here, we scrutinized how c-di-GMP affects molecular motor properties and adhesive behavior of T4P. By means of retraction, T4P generated forces of ∼ 30 pN. Deletion mutants in the proteins with known roles in biofilm formation, swarming motility and exopolysaccharide (EPS) production, specifically, the diguanulate cyclases sadC and roeA or the c-di-GMP phosphodiesterase bifA, showed only modest effects on velocity or force of T4P retraction...
February 6, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28163311/cyclic-di-gmp-second-messenger-extraordinaire
#11
REVIEW
Urs Jenal, Alberto Reinders, Christian Lori
Cyclic dinucleotides (CDNs) are highly versatile signalling molecules that control various important biological processes in bacteria. The best-studied example is cyclic di-GMP (c-di-GMP). Known since the late 1980s, it is now recognized as a near-ubiquitous second messenger that coordinates diverse aspects of bacterial growth and behaviour, including motility, virulence, biofilm formation and cell cycle progression. In this Review, we discuss important new insights that have been gained into the molecular principles of c-di-GMP synthesis and degradation, which are mediated by diguanylate cyclases and c-di-GMP-specific phosphodiesterases, respectively, and the cellular functions that are exerted by c-di-GMP-binding effectors and their diverse targets...
February 6, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28148244/detailed-analysis-of-c-di-gmp-mediated-regulation-of-csgd-expression-in-salmonella-typhimurium
#12
Irfan Ahmad, Annika Cimdins, Timo Beske, Ute Römling
BACKGROUND: The secondary messenger cyclic di-GMP promotes biofilm formation by up regulating the expression of csgD, encoding the major regulator of rdar biofilm formation in Salmonella typhimurium. The GGDEF/EAL domain proteins regulate the c-di-GMP turnover. There are twenty- two GGDEF/EAL domain proteins in the genome of S. typhimurium. In this study, we dissect the role of individual GGDEF/EAL proteins for csgD expression and rdar biofilm development. RESULTS: Among twelve GGDEF domains, two proteins upregulate and among fifteen EAL domains, four proteins down regulate csgD expression...
February 2, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28138140/hit-the-right-spots-cell-cycle-control-by-phosphorylated-guanosines-in-alphaproteobacteria
#13
REVIEW
Régis Hallez, Marie Delaby, Stefano Sanselicio, Patrick H Viollier
The class Alphaproteobacteria includes Gram-negative free-living, symbiotic and obligate intracellular bacteria, as well as important plant, animal and human pathogens. Recent work has established the key antagonistic roles that phosphorylated guanosines, cyclic-di-GMP (c-di-GMP) and the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p)ppGpp), have in the regulation of the cell cycle in these bacteria. In this Review, we discuss the insights that have been gained into the regulation of the initiation of DNA replication and cytokinesis by these second messengers, with a particular focus on the cell cycle of Caulobacter crescentus...
January 31, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28120848/nanogel-based-nasal-ghrelin-vaccine-prevents-obesity
#14
T Azegami, Y Yuki, S Sawada, M Mejima, K Ishige, K Akiyoshi, H Itoh, H Kiyono
Obesity is associated with multiple comorbidities such as cardiovascular diseases and has a huge economic impact on the health-care system. However, the treatment of obesity remains insufficient in terms of efficacy, tolerability, and safety. Here we created a nasal vaccine against obesity for the first time. To avoid the injectable administration-caused pain and skin-related adverse event, we focused on the intranasal route of antigen delivery. We developed a vaccine antigen (ghrelin-PspA (pneumococcal surface protein A)), which is a recombinant fusion protein incorporating ghrelin, a hormone that stimulates food intake and decreases energy expenditure, and PspA, a candidate of pneumococcal vaccine as a carrier protein...
January 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28078398/potential-coupling-effects-of-ammonia-oxidizing-and-anaerobic-ammonium-oxidizing-bacteria-on-completely-autotrophic-nitrogen-removal-over-nitrite-biofilm-formation-induced-by-the-second-messenger-cyclic-diguanylate
#15
Chao Wang, Sitong Liu, Xiaochen Xu, Chuanqi Zhao, Fenglin Yang, Dong Wang
The objective of this study was to investigate the influence of extracellular polymeric substance (EPS) on the coupling effects between ammonia-oxidizing bacteria (AOB) and anaerobic ammonium-oxidizing (anammox) bacteria for the completely autotrophic nitrogen removal over nitrite (CANON) biofilm formation in a moving bed biofilm reactor (MBBR). Analysis of the quantity of EPS and cyclic diguanylate (c-di-GMP) confirmed that the contents of polysaccharides and c-di-GMP were correlated in the AOB sludge, anammox sludge, and CANON biofilm...
January 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28057864/adenylate-cyclase-a-acting-on-pka-mediates-induction-of-stalk-formation-by-cyclic-diguanylate-at-the-dictyostelium-organizer
#16
Zhi-Hui Chen, Reema Singh, Christian Cole, Hajara Mohammed Lawal, Christina Schilde, Melanie Febrer, Geoffrey J Barton, Pauline Schaap
Coordination of cell movement with cell differentiation is a major feat of embryonic development. The Dictyostelium stalk always forms at the organizing tip, by a mechanism that is not understood. We previously reported that cyclic diguanylate (c-di-GMP), synthesized by diguanylate cyclase A (DgcA), induces stalk formation. Here we used transcriptional profiling of dgca- structures to identify target genes for c-di-GMP, and used these genes to investigate the c-di-GMP signal transduction pathway. We found that knockdown of cAMP-dependent protein kinase (PKA) activity in prestalk cells reduced stalk gene induction by c-di-GMP, whereas PKA activation bypassed the c-di-GMP requirement for stalk gene expression...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28031943/supramolecular-polymer-formation-by-cyclic-dinucleotides-and-intercalators-affects-dinucleotide-enzymatic-processing
#17
Shizuka Nakayama, Jie Zhou, Yue Zheng, Henryk Szmacinski, Herman O Sintim
BACKGROUND: Cyclic dinucleotides form supramolecular aggregates with intercalators, and this property could be utilized in nanotechnology and medicine. METHODS & RESULTS: Atomic force microscopy and electrophoretic mobility shift assays were used to show that cyclic diguanylic acid (c-di-GMP) forms G-wires in the presence of intercalators. The average fluorescence lifetime of thiazole orange, when bound to c-di-GMP was greater than when bound to DNA G-quadruplexes or dsDNA...
March 2016: Future Science OA
https://www.readbyqxmd.com/read/28031279/progress-in-understanding-the-molecular-basis-underlying-functional-diversification-of-cyclic-dinucleotide-turnover-proteins
#18
REVIEW
Ute Römling, Zhao-Xun Liang, J Maxwell Dow
Cyclic di-GMP was the first cyclic dinucleotide second messenger described, presaging the discovery of additional cyclic dinucleotide messengers in bacteria and eukaryotes. The GGDEF diguanylate cyclase (DGC) and EAL and HD-GYP phosphodiesterase (PDE) domains conduct the turnover of cyclic di-GMP. These three unrelated domains belong to superfamilies that exhibit significant variations in function, and they include both enzymatically active and inactive members, with a subset involved in synthesis and degradation of other cyclic dinucleotides...
March 1, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28011630/a-polycystin-type-transient-receptor-potential-trp-channel-that-is-activated-by-atp
#19
David Traynor, Robert R Kay
ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants...
February 15, 2017: Biology Open
https://www.readbyqxmd.com/read/27990276/recent-advances-in-understanding-streptomyces
#20
REVIEW
Keith F Chater
About 2,500 papers dated 2014-2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes...
2016: F1000Research
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