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https://www.readbyqxmd.com/read/27915292/the-dual-role-of-dksa-protein-in-the-regulation-of-escherichia-coli-pargx-promoter
#1
Robert Łyżeń, Amarnath Maitra, Klaudia Milewska, Maja Kochanowska-Łyżeń, V James Hernandez, Agnieszka Szalewska-Pałasz
Gene expression regulation by the stringent response effector, ppGpp, is facilitated by DksA protein; however DksA and ppGpp can play independent roles in transcription. In Escherichia coli, the pArgX promoter which initiates the transcription of four tRNA genes was shown to be inhibited by ppGpp. Our studies on the role of DksA in pArgX regulation revealed that it can stimulate transcription by increasing the binding of RNA polymerase to the promoter and the productive transcription complex formation. However, when DksA is present together with ppGpp a severe down-regulation of promoter activity is observed...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903898/transfer-rna-is-highly-unstable-during-early-amino-acid-starvation-in-escherichia-coli
#2
Sine Lo Svenningsen, Mette Kongstad, Thomas Søndergaard Stenum, Ana J Muñoz-Gómez, Michael A Sørensen
Due to its long half-life compared to messenger RNA, bacterial transfer RNA is known as stable RNA. Here, we show that tRNAs become highly unstable as part of Escherichia coli's response to amino acid starvation. Degradation of the majority of cellular tRNA occurs within twenty minutes of the onset of starvation for each of several amino acids. Both the non-cognate and cognate tRNA for the amino acid that the cell is starving for are degraded, and both charged and uncharged tRNA species are affected. The alarmone ppGpp orchestrates the stringent response to amino acid starvation...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27900286/selective-and-efficient-elimination-of-vibrio-cholerae-with-a-chemical-modulator-that-targets-glucose-metabolism
#3
Young Taek Oh, Hwa Young Kim, Eun Jin Kim, Junhyeok Go, Wontae Hwang, Hyoung Rae Kim, Dong Wook Kim, Sang Sun Yoon
Vibrio cholerae, a Gram-negative bacterium, is the causative agent of pandemic cholera. Previous studies have shown that the survival of the seventh pandemic El Tor biotype V. cholerae strain N16961 requires production of acetoin in a glucose-rich environment. The production of acetoin, a neutral fermentation end-product, allows V. cholerae to metabolize glucose without a pH drop, which is mediated by the production of organic acid. This finding suggests that inhibition of acetoin fermentation can result in V...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27875634/the-stringent-response-plays-a-key-role-in-bacillus-subtilis-survival-of-fatty-acid-starvation
#4
A A Pulschen, D E Sastre, F Machinandiarena, A Crotta Asis, D Albanesi, D de Mendoza, F J Gueiros-Filho
The stringent response is a universal adaptive mechanism to protect bacteria from nutritional and environmental stresses. The role of the stringent response during lipid starvation has been studied only in Gram-negative bacteria. Here we report that the stringent response also plays a crucial role in the adaptation of the model Gram-positive Bacillus subtilis to fatty acid starvation. B. subtilis lacking all three (p)ppGpp-synthetases (RelBs , RelP and RelQ) or bearing a RelBs variant that no longer synthesizes (p)ppGpp suffer extreme loss of viability upon lipid starvation...
November 22, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27819280/cationic-bactericidal-peptide-1018-does-not-specifically-target-the-stringent-response-alarmone-p-ppgpp
#5
Liis Andresen, Tanel Tenson, Vasili Hauryliuk
The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p)ppGpp (de la Fuente-Núñez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799328/the-%C3%AF-subunit-governs-rna-polymerase-stability-and-transcriptional-specificity-in-staphylococcus-aureus
#6
Andy Weiss, Brittney D Moore, Miguel H J Tremblay, Dale Chaput, Astrid Kremer, Lindsey N Shaw
Staphylococcus aureus is a major human pathogen that causes infection in a wide variety of sites within the human body. Its ability to adapt to the human host, and to produce a successful infection, requires precise orchestration of gene expression. While DNA-dependent RNA polymerase (RNAP) is generally well characterized, the role of several small accessory subunits within the complex has yet to be fully explored. This is particularly true for the omega (ω or RpoZ) subunit, which has been extensively studied in Gram-negative bacteria, but largely neglected in Gram-positive counterparts...
October 31, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27775002/auxotrophy-based-high-throughput-screening-assay-for-the-identification-of-bacillus-subtilis-stringent-response-inhibitors
#7
Liis Andresen, Vallo Varik, Yuzuru Tozawa, Steffi Jimmy, Stina Lindberg, Tanel Tenson, Vasili Hauryliuk
The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27768816/growth-phase-dependent-control-of-r27-conjugation-is-mediated-by-the-interplay-between-the-plasmid-encoded-regulatory-circuit-trhr-trhy-htda-and-the-camp-regulon
#8
Marta Gibert, Sonia Paytubi, Sergi Beltrán, Antonio Juárez, Carlos Balsalobre, Cristina Madrid
Plasmids of the incompatibility group HI1 (IncHI1) have been isolated from several Gram-negative pathogens and are associated with the spread of multidrug resistance. Their conjugation is tightly regulated and it is inhibited at temperatures higher than 30°C, indicating that conjugation occurs outside warm-blooded hosts. Using R27, the prototype of IncHI1 plasmids, we report that plasmid transfer efficiency in E. coli strongly depends on the physiological state of the donor cells. Conjugation frequency is high when cells are actively growing, dropping sharply when cells enter the stationary phase of growth...
October 21, 2016: Environmental Microbiology
https://www.readbyqxmd.com/read/27767957/factors-essential-for-l-d-transpeptidase-mediated-peptidoglycan-cross-linking-and-%C3%AE-lactam-resistance-in-escherichia-coli
#9
Jean-Emmanuel Hugonnet, Dominique Mengin-Lecreulx, Alejandro Monton, Tanneke den Blaauwen, Etienne Carbonnelle, Carole Veckerlé, Yves Brun, Michael van Nieuwenhze, Christiane Bouchier, Kuyek Tu, Louis B Rice, Michel Arthur
The target of β-lactam antibiotics is the D,D-transpeptidase activity of penicillin-binding proteins (PBPs) for synthesis of 4→3 cross-links in the peptidoglycan of bacterial cell walls. Unusual 3→3 cross-links formed by L,D-transpeptidases were first detected in Escherichia coli more than four decades ago, however no phenotype has previously been associated with their synthesis. Here we show that production of the L,D-transpeptidase YcbB in combination with elevated synthesis of the (p)ppGpp alarmone by RelA lead to full bypass of the D,D-transpeptidase activity of PBPs and to broad-spectrum β-lactam resistance...
October 21, 2016: ELife
https://www.readbyqxmd.com/read/27672159/hypothesis-type-i-toxin-antitoxin-genes-enter-the-persistence-field-a-feedback-mechanism-explaining-membrane-homoeostasis
#10
REVIEW
Kenn Gerdes
Bacteria form persisters, cells that are tolerant to multiple antibiotics and other types of environmental stress. Persister formation can be induced either stochastically in single cells of a growing bacterial ensemble, or by environmental stresses, such as nutrient starvation, in a subpopulation of cells. In many cases, the molecular mechanisms underlying persistence are still unknown. However, there is growing evidence that, in enterobacteria, both stochastically and environmentally induced persistence are controlled by the second messenger (p)ppGpp...
November 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27664726/role-of-ppgpp-in-pseudomonas-aeruginosa-acute-pulmonary-infection-and-virulence-regulation
#11
Xiaohui Xu, Hua Yu, Di Zhang, Junzhi Xiong, Jing Qiu, Rong Xin, Xiaomei He, Halei Sheng, Wenqiang Cai, Lu Jiang, Kebin Zhang, Xiaomei Hu
During infection, bacteria might generate adaptive responses to facilitate their survival and colonization in the host environment. The alarmone guanosine 5'-triphosphate-3'-diphosphate (ppGpp), the levels of which are regulated by the RelA and SpoT enzymes, plays a critical role in mediating bacterial adaptive responses and virulence. However, the mechanism by which ppGpp regulates virulence-associated traits in Pseudomonas aeruginosa is poorly understood. To investigate the regulatory role of ppGpp, the ppGpp-deficient strain ΔRS (relA and spoT gene double mutant) and the complemented strain ΔRS(++) (complemented with relA and spoT genes) were constructed...
November 2016: Microbiological Research
https://www.readbyqxmd.com/read/27658736/bacterial-abscess-formation-is-controlled-by-the-stringent-stress-response-and-can-be-targeted-therapeutically
#12
Sarah C Mansour, Daniel Pletzer, César de la Fuente-Núñez, Paul Kim, Gordon Y C Cheung, Hwang-Soo Joo, Michael Otto, Robert E W Hancock
Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model...
September 17, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27630635/rel-is-required-for-morphogenesis-of-resting-cells-in-mycobacterium-smegmatis
#13
Mu-Lu Wu, Chuu Ling Chan, Thomas Dick
Recently we showed that upon transfer of growing Mycobacterium smegmatis into saline, the bacilli exited the canonical cell division cycle and formed septated multi-nucleoided cells. Under shock starvation (i.e., in saline without any carbon source), differentiation terminated at this stage with internally remodeled Large Resting Cells (LARCs). Whereas under gentle starvation (i.e., in saline with trace amounts of a carbon source), the septated multi-nucleoided bacilli completed cell division and separated into mono-nucleoided Small Resting Cells (SMRCs)...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27618065/therapeutic-potential-of-gramicidin-s-in-the-treatment-of-root-canal-infections
#14
Marina Berditsch, Hannah Lux, Oleg Babii, Sergii Afonin, Anne S Ulrich
An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix(®) paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E...
September 7, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27558436/identification-and-functional-analysis-of-rela-spot-homolog-rsh-genes-in-deinococcus-radiodurans
#15
Jinhui Wang, Ye Tian, Zhengfu Zhou, Liwen Zhang, Wei Zhang, Min Lin, Min Chen
To identify the global effects of (p)ppGpp in a Gram-positive bacterium Deinococcus radiodurans, which exhibits remarkable resistance to radiation and other stresses, RSHs mutants constructed by direct deletion mutagenesis. The results showed that RelA has both synthesis and hydrolysis domains of (p)ppGpp, while RelQ only synthesizes (p)ppGpp in Deinococcus radiodurans. The growth assay for mutants and complementation analysis revealed that deletion of relA and relQ sensitized the cells to H₂O₂, heat shock, and amino acid limitation...
August 24, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27524648/-p-ppgpp-synthetases-regulate-the-pathogenesis-of-zoonotic-streptococcus-suis
#16
Jiawen Zhu, Tengfei Zhang, Zhipeng Su, Lu Li, Dong Wang, Ran Xiao, Muye Teng, Meifang Tan, Rui Zhou
(p)ppGpp-mediated stringent response is one of the main adaption mechanism in bacteria, and the ability to adapt to environment is linked to the pathogenesis of bacterial pathogens. In the zoonotic pathogen Streptococcus suis, there are two (p)ppGpp synthetases, RelA and RelQ. To investigate the regulatory functions of (p)ppGpp/(p)ppGpp synthetases on the pathogenesis of S. suis, the phenotypes of the [(p)ppGpp(0)] mutant ΔrelAΔrelQ and its parental strain were compared. Light and electron microscopy observation showed that the mutant strain had a longer chain-length than its parental strain...
October 2016: Microbiological Research
https://www.readbyqxmd.com/read/27516759/an-essential-role-for-p-ppgpp-in-the-integration-of-stress-tolerance-peptide-signaling-and-competence-development-in-streptococcus-mutans
#17
Justin Kaspar, Jeong N Kim, Sang-Joon Ahn, Robert A Burne
The microbes that inhabit the human oral cavity are subjected to constant fluctuations in their environment. To overcome these challenges and gain a competitive advantage, oral streptococci employ numerous adaptive strategies, many of which appear to be intertwined with the development of genetic competence. Here, we demonstrate that the regulatory circuits that control development of competence in Streptococcus mutans, a primary etiological agent of human dental caries, are integrated with key stress tolerance pathways by the molecular alarmone (p)ppGpp...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27506217/evaluation-of-the-characteristics-of-leucyl-trna-synthetase-leurs-inhibitor-an3365-in-combination-with-different-antibiotic-classes
#18
C G Monteferrante, A Jirgensons, V Varik, V Hauryliuk, W H F Goessens, J P Hays
Aminoacyl tRNA synthetases are enzymes involved in the key process of coupling an amino acid to its cognate tRNA. AN3365 is a novel antibiotic that specifically targets leucyl-tRNA synthetase, whose development was halted after evaluation in phase II clinical trials owing to the rapid selection of resistance. In an attempt to bring AN3365 back into the developmental pipeline we have evaluated the efficacy of AN3365 in combination with different classes of antibiotic and characterized its mechanism of action...
November 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27486247/the-stringent-response-regulates-adaptation-to-darkness-in-the-cyanobacterium-synechococcus-elongatus
#19
Rachel D Hood, Sean A Higgins, Avi Flamholz, Robert J Nichols, David F Savage
The cyanobacterium Synechococcus elongatus relies upon photosynthesis to drive metabolism and growth. During darkness, Synechococcus stops growing, derives energy from its glycogen stores, and greatly decreases rates of macromolecular synthesis via unknown mechanisms. Here, we show that the stringent response, a stress response pathway whose genes are conserved across bacteria and plant plastids, contributes to this dark adaptation. Levels of the stringent response alarmone guanosine 3'-diphosphate 5'-diphosphate (ppGpp) rise after a shift from light to dark, indicating that darkness triggers the same response in cyanobacteria as starvation in heterotrophic bacteria...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27471495/growth-of-streptococcus-mutans-in-biofilms-alters-peptide-signaling-at-the-sub-population-level
#20
Robert C Shields, Robert A Burne
Streptococcus mutans activates multiple cellular processes in response to the formation of a complex between comX-inducing peptide (XIP) and the ComR transcriptional regulator. Bulk phase and microfluidic experiments previously revealed that ComR-dependent activation of comX is altered by pH and by carbohydrate source. Biofilm formation is a major factor in bacterial survival and virulence in the oral cavity. Here, we sought to determine the response of S. mutans biofilm cells to XIP during different stages of biofilm maturation...
2016: Frontiers in Microbiology
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