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https://www.readbyqxmd.com/read/28820325/small-alarmone-synthetases-as-novel-bacterial-rna-binding-proteins
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28678862/pseudomonas-aeruginosa-cells-attached-to-a-surface-display-a-typical-proteome-early-as-20-minutes-of-incubation
#4
Marc Crouzet, Stéphane Claverol, Anne-Marie Lomenech, Caroline Le Sénéchal, Patricia Costaglioli, Christophe Barthe, Bertrand Garbay, Marc Bonneu, Sébastien Vilain
Biofilms are present in all environments and often result in negative effects due to properties of the biofilm lifestyle and especially antibiotics resistance. Biofilms are associated with chronic infections. Controlling bacterial attachment, the first step of biofilm formation, is crucial for fighting against biofilm and subsequently preventing the persistence of infection. Thus deciphering the underlying molecular mechanisms involved in attachment could allow discovering molecular targets from it would be possible to develop inhibitors against bacterial colonization and potentiate antibiotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28652326/trar-directly-regulates-transcription-initiation-by-mimicking-the-combined-effects-of-the-global-regulators-dksa-and-ppgpp
#5
Saumya Gopalkrishnan, Wilma Ross, Albert Y Chen, Richard L Gourse
The Escherichia coli F element-encoded protein TraR is a distant homolog of the chromosome-encoded transcription factor DksA. Here we address the mechanism by which TraR acts as a global regulator, inhibiting some promoters and activating others. We show that TraR regulates transcription directly in vitro by binding to the secondary channel of RNA polymerase (RNAP) using interactions similar, but not identical, to those of DksA. Even though it binds to RNAP with only slightly higher affinity than DksA and is only half the size of DksA, TraR by itself inhibits transcription as strongly as DksA and ppGpp combined and much more than DksA alone...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28633201/rapid-start-up-of-denitrifying-granular-sludge-by-dosing-with-semi-starvation-fluctuation-c-n-ratio-strategy
#6
Wenyu Niu, Jianbo Guo, Jing Lian, Yuanyuan Song, Caicai Lu, Haibo Li, Yi Han, Pengna Yin
This study cultivated denitrifying granular sludge in three UASB reactors by the semi-starvation fluctuation C/N ratio strategy (reactor 1 (R1): constant C/N ratio; R2: regular fluctuation C/N ratio; and R3: semi-starvation fluctuation C/N ratio (SSF)). Microbial aggregates appeared in R1, R2 and R3 on days 28, 14 and 6, respectively. Compared with the results in R1 and R2, the guanosine tetraphosphate (ppGpp) concentration was highest, the acyl homoserine lactones (AHLs) concentration quickly reached a certain threshold, and more protein (PN) of extracellular polymeric substances (EPS) secretion resulted in the rapid formation of denitrifying granular sludge in R3...
October 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28624614/gene-transfer-agent-promotes-evolvability-within-the-fittest-subpopulation-of-a-bacterial-pathogen
#7
Maxime Québatte, Matthias Christen, Alexander Harms, Jonas Körner, Beat Christen, Christoph Dehio
The Bartonella gene transfer agent (BaGTA) is an archetypical example for domestication of a phage-derived element to permit high-frequency genetic exchange in bacterial populations. Here we used multiplexed transposon sequencing (TnSeq) and single-cell reporters to globally define the core components and transfer dynamics of BaGTA. Our systems-level analysis has identified inner- and outer-circle components of the BaGTA system, including 55 regulatory components, as well as an additional 74 and 107 components mediating donor transfer and recipient uptake functions...
June 28, 2017: Cell Systems
https://www.readbyqxmd.com/read/28611182/the-lost-language-of-the-rna-world
#8
REVIEW
James W Nelson, Ronald R Breaker
The possibility of an RNA World is based on the notion that life on Earth passed through a primitive phase without proteins, a time when all genomes and enzymes were composed of ribonucleic acids. Numerous apparent vestiges of this ancient RNA World remain today, including many nucleotide-derived coenzymes, self-processing ribozymes, metabolite-binding riboswitches, and even ribosomes. Many of the most common signaling molecules and second messengers used by modern organisms are also formed from RNA nucleotides or their precursors...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28602657/fatty-acid-availability-sets-cell-envelope-capacity-and-dictates-microbial-cell-size
#9
Stephen Vadia, Jessica L Tse, Rafael Lucena, Zhizhou Yang, Douglas R Kellogg, Jue D Wang, Petra Anne Levin
Nutrients-and by extension biosynthetic capacity-positively impact cell size in organisms throughout the tree of life. In bacteria, cell size is reduced 3-fold in response to nutrient starvation or accumulation of the alarmone ppGpp, a global inhibitor of biosynthesis. However, whether biosynthetic capacity as a whole determines cell size or whether particular anabolic pathways are more important than others remains an open question. Here we identify fatty acid synthesis as the primary biosynthetic determinant of Escherichia coli size and present evidence supporting a similar role for fatty acids as a positive determinant of size in the Gram-positive bacterium Bacillus subtilis and the single-celled eukaryote Saccharomyces cerevisiae...
June 19, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28597815/dksa-hapr-rpos-axis-regulates-haemagglutinin-protease-production-in-vibrio-cholerae
#10
Pallabi Basu, Ritesh Ranjan Pal, Shreya Dasgupta, Rupak K Bhadra
DksA acts as a co-factor for the intracellular small signalling molecule ppGpp during the stringent response. We recently reported that the expression of the haemagglutinin protease (HAP), which is needed for shedding of the cholera pathogen Vibrio cholerae during the late phase of infection, is significantly downregulated in V. cholerae ∆dksA mutant (∆dksAVc) cells. So far, it has been shown that HAP production by V. cholerae cells is critically regulated by HapR and also by RpoS. Here, we provide evidence that V...
June 8, 2017: Microbiology
https://www.readbyqxmd.com/read/28587697/ppgpp-and-cytotoxicity-diversity-in-shiga-toxin-producing-escherichia-coli-stec-isolates
#11
A E Stella, D Luz Hessel DA Cunha, R M F Piazza, B Spira
Shiga toxin-producing Escherichia coli (STEC) is a known food pathogen, which main reservoir is the intestine of ruminants. The abundance of different STEC lineages in nature reflect a heterogeneity that is characterised by the differential expression of certain genotypic characteristics, which in turn are influenced by the environmental conditions to which the microorganism is exposed. Bacterial homeostasis and stress response are under the control of the alarmone guanosine tetraphosphate (ppGpp), which intrinsic levels varies across the E...
August 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28575317/ribosomal-selection-of-mrnas-with-degenerate-initiation-triplets
#12
He Chengguang, Paola Sabatini, Letizia Brandi, Anna M Giuliodori, Cynthia L Pon, Claudio O Gualerzi
To assess the influence of degenerate initiation triplets on mRNA recruitment by ribosomes, five mRNAs identical but for their start codon (AUG, GUG, UUG, AUU and AUA) were offered to a limiting amount of ribosomes, alone or in competition with an identical AUGmRNA bearing a mutation conferring different electrophoretic mobility to the product. Translational efficiency and competitiveness of test mRNAs toward this AUGmRNA were determined quantifying the relative amounts of the electrophoretically separated wt and mutated products synthesized in vitro and found to be influenced to different extents by the nature of their initiation triplet and by parameters such as temperature and nutrient availability in the medium...
May 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28536785/significance-of-accumulation-of-the-alarmone-p-ppgpp-in-chloroplasts-for-controlling-photosynthesis-and-metabolite-balance-during-nitrogen-starvation-in-arabidopsis
#13
Rina Honoki, Sumire Ono, Akira Oikawa, Kazuki Saito, Shinji Masuda
The regulatory nucleotides, guanosine 5'-triphosphate 3'-diphosphate (pppGpp) and guanosine 5'-diphosphate 3'-diphosphate (ppGpp), were originally identified in Escherichia coli, and control a large set of gene expression and enzyme activities. The (p)ppGpp-dependent control of cell activities is referred to as the stringent response. A growing number of (p)ppGpp synthase/hydrolase homologs have been identified in plants, which are localized in plastids in Arabidopsis thaliana. We recently reported that the Arabidopsis mutant overproducing ppGpp in plastids showed dwarf chloroplasts, and transcript levels in the mutant plastids were significantly suppressed...
May 23, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28483855/association-of-metal-homeostasis-and-p-ppgpp-regulation-in-the-pathophysiology-of-enterococcus-faecalis
#14
C Colomer-Winter, A O Gaca, J A Lemos
In Enterococcus faecalis, the regulatory nucleotides pppGpp and ppGpp, collectively, (p)ppGpp, are required for growth in blood, survival within macrophages, and virulence. However, a clear understanding of how (p)ppGpp promotes virulence in E. faecalis and other bacterial pathogens is still lacking. In the host, the essential transition metals iron (Fe) and manganese (Mn) are not readily available to invading pathogens because of a host-driven process called nutritional immunity. Considering its central role in adaptation to nutritional stresses, we hypothesized that (p)ppGpp mediates E...
July 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28455332/absence-of-ppgpp-leads-to-increased-mobilization-of-intermediately-accumulated-poly-3-hydroxybutyrate-in-ralstonia-eutropha-h16
#15
Janina R Juengert, Marina Borisova, Christoph Mayer, Christiane Wolz, Christopher J Brigham, Anthony J Sinskey, Dieter Jendrossek
In this study, we constructed a set of Ralstonia eutropha H16 strains with single, double, or triple deletions of the (p)ppGpp synthase/hydrolase (spoT1), (p)ppGpp synthase (spoT2), and/or polyhydroxybutyrate (PHB) depolymerase (phaZa1 or phaZa3) gene, and we determined the impact on the levels of (p)ppGpp and on accumulated PHB. Mutants with deletions of both the spoT1 and spoT2 genes were unable to synthesize detectable amounts of (p)ppGpp and accumulated only minor amounts of PHB, due to PhaZa1-mediated depolymerization of PHB...
July 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28447391/transcriptional-response-of-escherichia-coli-to-ammonia-and-glucose-fluctuations
#16
Joana Danica Simen, Michael Löffler, Günter Jäger, Karin Schäferhoff, Andreas Freund, Jakob Matthes, Jan Müller, Ralf Takors
In large-scale production processes, metabolic control is typically achieved by limited supply of essential nutrients such as glucose or ammonia. With increasing bioreactor dimensions, microbial producers such as Escherichia coli are exposed to changing substrate availabilities due to limited mixing. In turn, cells sense and respond to these dynamic conditions leading to frequent activation of their regulatory programmes. Previously, we characterized short- and long-term strategies of cells to adapt to glucose fluctuations...
July 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28438933/pyrazinoic-acid-inhibits-a-bifunctional-enzyme-in-mycobacterium-tuberculosis
#17
Moses Njire, Na Wang, Bangxing Wang, Yaoju Tan, Xingshan Cai, Yanwen Liu, Julius Mugweru, Jintao Guo, H M Adnan Hameed, Shouyong Tan, Jianxiong Liu, Wing Wai Yew, Eric Nuermberger, Gyanu Lamichhane, Jinsong Liu, Tianyu Zhang
Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug into pyrazinoic acid (POA) by Mycobacterium tuberculosis has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report how a new PZA resistance determinant, the Asp67Asn substitution in Rv2783, confers M. tuberculosis resistance to PZA. Expression of the mutant allele but not the wild-type allele in M...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28396544/synthetic-p-ppgpp-analogue-is-an-inhibitor-of-stringent-response-in-mycobacteria
#18
Kirtimaan Syal, Kelly Flentie, Neerupma Bhardwaj, Krishnagopal Maiti, Narayanaswamy Jayaraman, Christina L Stallings, Dipankar Chatterji
Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria...
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28388876/transcriptomic-buffering-of-cryptic-genetic-variation-contributes-to-meningococcal-virulence
#19
Biju Joseph Ampattu, Laura Hagmann, Chunguang Liang, Marcus Dittrich, Andreas Schlüter, Jochen Blom, Elizaveta Krol, Alexander Goesmann, Anke Becker, Thomas Dandekar, Tobias Müller, Christoph Schoen
BACKGROUND: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence...
April 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28320944/negative-allosteric-regulation-of-enterococcus-faecalis-small-alarmone-synthetase-relq-by-single-stranded-rna
#20
Jelena Beljantseva, Pavel Kudrin, Liis Andresen, Victoria Shingler, Gemma C Atkinson, Tanel Tenson, Vasili Hauryliuk
The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, pathogenicity, and antibiotic tolerance. We show that the tetrameric small alarmone synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis is a sequence-specific RNA-binding protein. RelQ's enzymatic and RNA binding activities are subject to intricate allosteric regulation. (p)ppGpp synthesis is potently inhibited by the binding of single-stranded RNA...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
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