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https://www.readbyqxmd.com/read/29135333/challenges-of-ligand-identification-for-the-second-wave-of-orphan-riboswitch-candidates
#1
Etienne B Greenlee, Shira Stav, Ruben M Atilho, Kenneth I Brewer, Kimberly A Harris, Sarah N Malkowski, Gayan Mirihana Arachchilage, Kevin R Perkins, Madeline E Sherlock, Ronald R Breaker
Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn(2+), and the metabolites guanidine and PRPP...
November 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/29061665/dksa-and-ppgpp-regulate-the-%C3%AF-s-stress-response-by-activating-promoters-for-the-small-rna-dsra-and-the-anti-adapter-protein-irap
#2
Mary E Girard, Saumya Gopalkrishnan, Elicia D Grace, Jennifer A Halliday, Richard L Gourse, Christophe Herman
σ(S) is an alternative sigma factor, encoded by the rpoS gene, that redirects cellular transcription to a large family of genes in response to stressful environmental signals. This so-called σ(S) general stress response is necessary for survival in many bacterial species and is controlled by a complex, multifactorial pathway that regulates σ(S) levels transcriptionally, translationally, and post-translationally in Escherichia coli It was shown previously that the transcription factor DksA and its cofactor ppGpp are among the many factors governing σ(S) synthesis, thus playing an important role in activation of the σ(S) stress response...
October 23, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/29034854/whole-genome-transcriptomics-reveals-global-effects-including-up-regulation-of-francisella-pathogenicity-island-gene-expression-during-active-stringent-response-in-the-highly-virulent-francisella-tularensis-subsp-tularensis-schu-s4
#3
Amber L Murch, Paul J Skipp, Peter L Roach, Petra C F Oyston
During conditions of nutrient limitation bacteria undergo a series of global gene expression changes to survive conditions of amino acid and fatty acid starvation. Rapid reallocation of cellular resources is brought about by gene expression changes coordinated by the signalling nucleotides' guanosine tetraphosphate or pentaphosphate, collectively termed (p)ppGpp and is known as the stringent response. The stringent response has been implicated in bacterial virulence, with elevated (p)ppGpp levels being associated with increased virulence gene expression...
October 16, 2017: Microbiology
https://www.readbyqxmd.com/read/29027458/the-stringent-response-induced-by-phosphate-limitation-promotes-purine-salvage-in-agrobacterium-fabrum
#4
Smitha Sivapragasam, Dinesh K Deochand, Jacob K Meariman, Anne Grove
Agrobacterium fabrum induces tumor growth in susceptible plant species. The upregulation of virulence genes that occurs when the bacterium senses plant-derived compounds is enhanced by acidic pH and limiting inorganic phosphate. Nutrient starvation may also trigger the stringent response, and purine salvage is among the pathways expected to be favored under such conditions. We show here that phosphate limitation induces the stringent response, as evidenced by production of (p)ppGpp, and that the xdhCSML operon encoding the purine salvage enzyme xanthine dehydrogenase is upregulated ∼15-fold...
October 31, 2017: Biochemistry
https://www.readbyqxmd.com/read/29021784/synthetic-peptides-to-target-stringent-response-controlled-virulence-in-a-pseudomonas-aeruginosa-murine-cutaneous-infection-model
#5
Daniel Pletzer, Heidi Wolfmeier, Manjeet Bains, Robert E W Hancock
Microorganisms continuously monitor their surroundings and adaptively respond to environmental cues. One way to cope with various stress-related situations is through the activation of the stringent stress response pathway. In Pseudomonas aeruginosa this pathway is controlled and coordinated by the activity of the RelA and SpoT enzymes that metabolize the small nucleotide secondary messenger molecule (p)ppGpp. Intracellular ppGpp concentrations are crucial in mediating adaptive responses and virulence. Targeting this cellular stress response has recently been the focus of an alternative approach to fight antibiotic resistant bacteria...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28986449/mfd-translocase-is-necessary-and-sufficient-for-transcription-coupled-repair-in-escherichia-coli
#6
Ogun Adebali, Aziz Sancar, Christopher P Selby
Nucleotide excision repair in Escherichia coli is stimulated by transcription, specifically in the transcribed strand. Previously, it was shown that this transcription-coupled repair (TCR) is mediated by the Mfd translocase. Recently, it was proposed that in fact the majority of TCR in E. coli is catalyzed by a second pathway ("backtracking-mediated TCR") that is dependent on the UvrD helicase and the guanosine pentaphosphate (ppGpp) alarmone/stringent response regulator. Recently, we reported that as measured by the excision repair-sequencing (XR-seq), UvrD plays no role in TCR genome-wide...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28986375/stringent-response-regulators-contribute-to-the-recovery-from-glucose-phosphate-stress-in-escherichia-coli
#7
Julie R Kessler, Brandi L Cobe, Gregory R Richards
In enteric bacteria like Escherichia coli, the transcription factor SgrR and the small RNA SgrS regulate the response to glucose-phosphate stress, a metabolic dysfunction that results in growth inhibition and stems from the intracellular accumulation of sugar-phosphates. SgrR activates transcription of sgrS, and SgrS helps to rescue cells from stress in part by inhibiting uptake of stressor sugar-phosphates. While the regulatory targets of this stress response are well described, less is known about how the SgrR-SgrS response itself is regulated...
October 6, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28979246/variable-persister-gene-interactions-with-p-ppgpp-for-persister-formation-in-escherichia-coli
#8
Shuang Liu, Nan Wu, Shanshan Zhang, Youhua Yuan, Wenhong Zhang, Ying Zhang
Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA) system HipAB depends on stringent response effector (p)ppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (p)ppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ) using Escherichia coli as a model...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28965178/integration-of-multiple-stimuli-sensing-systems-to-regulate-hrps-and-type-iii-secretion-system-in-erwinia-amylovora
#9
Jae Hoon Lee, Youfu Zhao
The bacterial enhancer binding protein (bEBP) HrpS is essential for Erwinia amylovora virulence by activating the type III secretion system (T3SS). However, how the hrpS gene is regulated remains poorly understood in E. amylovora. In this study, 5' rapid amplification of cDNA ends and promoter deletion analyses showed that the hrpS gene contains two promoters driven by HrpX/HrpY and the Rcs phosphorelay system, respectively. Electrophoretic mobility shift and gene expression assays demonstrated that integration host factor IHF positively regulates hrpS expression through directly binding the hrpX promoter and positively regulating hrpX/hrpY expression...
September 30, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28948393/within-and-beyond-the-stringent-response-rsh-and-p-ppgpp-in-plants
#10
REVIEW
Justyna Boniecka, Justyna Prusińska, Grażyna B Dąbrowska, Anna Goc
Plant RSH proteins are able to synthetize and/or hydrolyze unusual nucleotides called (p)ppGpp or alarmones. These molecules regulate nuclear and chloroplast transcription, chloroplast translation and plant development and stress response. Homologs of bacterial RelA/SpoT proteins, designated RSH, and products of their activity, (p)ppGpp-guanosine tetra-and pentaphosphates, have been found in algae and higher plants. (p)ppGpp were first identified in bacteria as the effectors of the stringent response, a mechanism that orchestrates pleiotropic adaptations to nutritional deprivation and various stress conditions...
November 2017: Planta
https://www.readbyqxmd.com/read/28891458/ppgpp-and-cytotoxicity-diversity-in-shiga-toxin-producing-escherichia-coli-stec-isolates-corrigendum
#11
A E Stella, D Luz, R M F Piazza, B Spira
No abstract text is available yet for this article.
September 11, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28887466/hplc-based-quantification-of-bacterial-housekeeping-nucleotides-and-alarmone-messengers-ppgpp-and-pppgpp
#12
Vallo Varik, Sofia Raquel Alves Oliveira, Vasili Hauryliuk, Tanel Tenson
Here we describe an HPLC-based method to quantify bacterial housekeeping nucleotides and the signaling messengers ppGpp and pppGpp. We have replicated and tested several previously reported HPLC-based approaches and assembled a method that can process 50 samples in three days, thus making kinetically resolved experiments feasible. The method combines cell harvesting by rapid filtration, followed by acid extraction, freeze-drying with chromatographic separation. We use a combination of C18 IPRP-HPLC (GMP unresolved and co-migrating with IMP; GDP and GTP; AMP, ADP and ATP; CTP; UTP) and SAX-HPLC in isocratic mode (ppGpp and pppGpp) with UV detection...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871248/identification-and-functional-characterization-of-small-alarmone-synthetases-in-corynebacterium-glutamicum
#13
Matthias Ruwe, Jörn Kalinowski, Marcus Persicke
The hyperphosphorylated guanosine derivatives ppGpp and pppGpp represent global regulators of the bacterial stress response, as they act as central elements of the stringent response system. Although it was assumed that both, (p)ppGpp synthesis and hydrolysis, are catalyzed by one bifunctional RSH-protein in the actinobacterial model organism Corynebacterium glutamicum ATCC 13032, two putative short alarmone synthetases (SASs) were identified by bioinformatic analyses. The predicted sequences of both enzymes, designated as RelP(*)Cg and RelSCg, exhibit high similarities to the conserved (p)ppGpp synthetase catalytic domain...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28870288/influence-of-p-ppgpp-on-biofilm-regulation-in-pseudomonas-putida-kt2440
#14
Huizhong Liu, Yujie Xiao, Hailing Nie, Qiaoyun Huang, Wenli Chen
The global regulatory molecule (p)ppGpp is synthesized under limited nutrition conditions and involves in many cellular processes in bacteria. (p)ppGpp has been reported to affect biofilm formation in several bacterial species. Here, we found that deletion of (p)ppGpp synthase genes of Pseudomonas putida KT2440 led to enhanced biofilm formation in polystyrene microtitre plates. Besides, the pellicle of this mutant formed at the air-liquid interface lost the robust structure and became frail. The biofilm formation and its structure are mainly determined by exopolysaccharides (EPSs) and adhesins...
November 2017: Microbiological Research
https://www.readbyqxmd.com/read/28864445/dissection-of-the-molecular-circuitry-controlling-virulence-in-francisella-tularensis
#15
Bonnie J Cuthbert, Wilma Ross, Amy E Rohlfing, Simon L Dove, Richard L Gourse, Richard G Brennan, Maria A Schumacher
Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, F. tularensis is classified as a category A bioweapon by the US government. F. tularensis virulence stems from genes encoded on the Francisella pathogenicity island (FPI). An unusual set of Francisella regulators-the heteromeric macrophage growth locus protein A (MglA)-stringent starvation protein A (SspA) complex and the DNA-binding protein pathogenicity island gene regulator (PigR)-activates FPI transcription and thus is essential for virulence...
August 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28854732/synchronized-switching-of-multiple-toxin-antitoxin-modules-by-p-ppgpp-fluctuation
#16
Chengzhe Tian, Szabolcs Semsey, Namiko Mitarai
Toxin-antitoxin (TA) loci are widespread in bacteria including important pathogenic species. Recent studies suggest that TA systems play a key role in persister formation. However, the persistence phenotype shows only weak dependence on the number of TA systems, i.e. they are functionally redundant. We use a mathematical model to investigate the interaction of multiple TA systems in the switching between growth and persistence. We explore two scenarios: (i) TA systems are bistable and each TA system experiences its own noise and (ii) the noise in the level of common stress signal (e...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28836724/sleeper-cells-the-stringent-response-and-persistence-in-the-borreliella-borrelia-burgdorferi-enzootic-cycle
#17
REVIEW
Felipe C Cabello, Henry P Godfrey, Julia V Bugrysheva, Stuart A Newman
Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B...
August 24, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28820325/small-alarmone-synthetases-as-novel-bacterial-rna-binding-proteins
#18
Vasili Hauryliuk, Gemma C Atkinson
The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, antibiotic tolerance and pathogenicity. We have recently shown that the Small Alarmone Synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis has an RNA-binding activity (Beljantseva et al. 2017). RelQ's activities as an enzyme and as a RNA-binding protein are mutually incompatible: binding of single-stranded RNA potently inhibits (p)ppGpp synthesis in a sequence-specific manner, and RelQ's enzymatic activity destabilizes the RNA:RelQ complex...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28750057/bactericidal-activity-of-alpha-bromocinnamaldehyde-against-persisters-in-escherichia-coli
#19
Qingshan Shen, Wei Zhou, Liangbin Hu, Yonghua Qi, Hongmei Ning, Jian Chen, Haizhen Mo
Persisters are tolerant to multiple antibiotics, and widely distributed in bacteria, fungi, parasites, and even cancerous human cell populations, leading to recurrent infections and relapse after therapy. In this study, we investigated the potential of cinnamaldehyde and its derivatives to eradicate persisters in Escherichia coli. The results showed that 200 μg/ml of alpha-bromocinnamaldehyde (Br-CA) was capable of killing all E. coli cells during the exponential phase. Considering the heterogeneous nature of persisters, multiple types of persisters were induced and exposed to Br-CA...
2017: PloS One
https://www.readbyqxmd.com/read/28743817/bacterial-signaling-nucleotides-inhibit-yeast-cell-growth-by-impacting-mitochondrial-and-other-specifically-eukaryotic-functions
#20
Andy Hesketh, Marta Vergnano, Chris Wan, Stephen G Oliver
We have engineered Saccharomyces cerevisiae to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP...
July 25, 2017: MBio
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