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https://www.readbyqxmd.com/read/28067906/prophage-mediated-defence-against-viral-attack-and-viral-counter-defence
#1
Rebekah M Dedrick, Deborah Jacobs-Sera, Carlos A Guerrero Bustamante, Rebecca A Garlena, Travis N Mavrich, Welkin H Pope, Juan C Cervantes Reyes, Daniel A Russell, Tamarah Adair, Richard Alvey, J Alfred Bonilla, Jerald S Bricker, Bryony R Brown, Deanna Byrnes, Steven G Cresawn, William B Davis, Leon A Dickson, Nicholas P Edgington, Ann M Findley, Urszula Golebiewska, Julianne H Grose, Cory F Hayes, Lee E Hughes, Keith W Hutchison, Sharon Isern, Allison A Johnson, Margaret A Kenna, Karen K Klyczek, Catherine M Mageeney, Scott F Michael, Sally D Molloy, Matthew T Montgomery, James Neitzel, Shallee T Page, Marie C Pizzorno, Marianne K Poxleitner, Claire A Rinehart, Courtney J Robinson, Michael R Rubin, Joseph N Teyim, Edwin Vazquez, Vassie C Ware, Jacqueline Washington, Graham F Hatfull
Temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses that infect mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that are either closely related (homotypic defence) or unrelated (heterotypic defence) to the prophage...
January 9, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28056744/nucleotide-second-messenger-signaling-as-a-target-for-the-control-of-bacterial-biofilm-formation
#2
Alberto J Martín-Rodríguez, Ute Römling
Bacterial biofilm formation and associated phenotypes are the major cause of chronic infection in humans. The major regulator of biofilm formation in Gram-negative and Gram-positive bacteria are nucleotide-based second messenger signaling pathways. Nucleotide-based signaling is a ubiquitous signal transduction mechanism in all domains of life that relay changes in the extracellular or intracellular milieu to protein or RNA effectors, leading to adaptive physiological responses. To date, six bona fide nucleotide signaling pathways, (p)ppGpp, cAMP, cGMP, c-di-AMP, c-di-GMP and cGAMP, have been characterized with respect to basic pathway modules and phenotypic and physiological output...
January 5, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28049149/rela-mutant-enterococcus-faecium-with-multiantibiotic-tolerance-arising-in-an-immunocompromised-host
#3
Erin S Honsa, Vaughn S Cooper, Mohammed N Mhaissen, Matthew Frank, Jessica Shaker, Amy Iverson, Jeffrey Rubnitz, Randall T Hayden, Richard E Lee, Charles O Rock, Elaine I Tuomanen, Joshua Wolf, Jason W Rosch
: Serious bacterial infections in immunocompromised patients require highly effective antibacterial therapy for cure, and thus, this setting may reveal novel mechanisms by which bacteria circumvent antibiotics in the absence of immune pressure. Here, an infant with leukemia developed vancomycin-resistant Enterococcus faecium (VRE) bacteremia that persisted for 26 days despite appropriate antibiotic therapy. Sequencing of 22 consecutive VRE isolates identified the emergence of a single missense mutation (L152F) in relA, which constitutively activated the stringent response, resulting in elevated baseline levels of the alarmone guanosine tetraphosphate (ppGpp)...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28024527/in-silico-prediction-of-dual-function-of-dksa-like-hypothetical-protein-in-v-cholerae-o395-genome
#4
Avirup Dutta, Atul Katarkar, Keya Chaudhuri
Cholera, an acute infection of the small intestine, is caused by Vibrio cholerae. The present study identified a hypothetical protein in V. cholerae O395, which was predicted to be acquired through horizontal gene transfer the origin of which was found to be from a phage. Its expression was further confirmed by RT-PCR. Homology based 3D model of the hypothetical protein indicated DksA like homologue. Protein binding site of 3D-model revealed a deep cleft which may influence the dimer formation and interaction with ds-DNA molecule...
January 2017: Microbiological Research
https://www.readbyqxmd.com/read/27986825/vitamin-c-targets-p-ppgpp-synthesis-leading-to-stalling-of-long-term-survival-and-biofilm-formation-in-m-smegmatis
#5
Kirtimaan Syal, Neerupma Bhardwaj, Dipankar Chatterji
Earlier, Vitamin C was demonstrated to sterilize Mycobacterium tuberculosis culture via Fenton's reaction at high concentration. It alters the regulatory pathways associated with stress response and dormancy. Since (p)ppGpp is considered to be the master regulator of stress response and is responsible for bacterial survival under stress, we tested the effect of Vitamin C on the formation of (p)ppGpp. In-vivo estimation of (p)ppGpp showed a decrease in (p)ppGpp levels in Vitamin C treated M. smegmatis cells in comparison to the untreated cells...
December 15, 2016: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/27980159/mechanisms-of-bacterial-persistence-during-stress-and-antibiotic-exposure
#6
REVIEW
Alexander Harms, Etienne Maisonneuve, Kenn Gerdes
Bacterial persister cells avoid antibiotic-induced death by entering a physiologically dormant state and are considered a major cause of antibiotic treatment failure and relapsing infections. Such dormant cells form stochastically, but also in response to environmental cues, by various pathways that are usually controlled by the second messenger (p)ppGpp. For example, toxin-antitoxin modules have been shown to play a major role in persister formation in many model systems. More generally, the diversity of molecular mechanisms driving persister formation is increasingly recognized as the cause of physiological heterogeneity that underlies collective multistress and multidrug tolerance of persister subpopulations...
December 16, 2016: Science
https://www.readbyqxmd.com/read/27956500/inhibiting-translation-elongation-can-aid-genome-duplication-in-escherichia-coli
#7
Kamila K Myka, Michelle Hawkins, Aisha H Syeda, Milind K Gupta, Caroline Meharg, Mark S Dillingham, Nigel J Savery, Robert G Lloyd, Peter McGlynn
Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an aminoacyl tRNA synthetase, AspRS, and in a translation factor needed for efficient proline-proline bond formation, EF-P, suppress Δrep ΔuvrD lethality. Thus replication-transcription conflicts can be alleviated by the partial sacrifice of a mechanism that reduces replicative barriers, namely translating ribosomes that reduce RNA polymerase backtracking...
December 11, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27933045/what-is-the-link-between-stringent-response-endoribonuclease-encoding-type-ii-toxin-antitoxin-systems-and-persistence
#8
Bhaskar C M Ramisetty, Dimpy Ghosh, Maoumita Roy Chowdhury, Ramachandran S Santhosh
Persistence is a transient and non-inheritable tolerance to antibiotics by a small fraction of a bacterial population. One of the proposed determinants of bacterial persistence is toxin-antitoxin systems (TASs) which are also implicated in a wide range of stress-related phenomena. Maisonneuve E, Castro-Camargo M, Gerdes K. 2013. Cell 154:1140-1150 reported an interesting link between ppGpp mediated stringent response, TAS, and persistence. It is proposed that accumulation of ppGpp enhances the accumulation of inorganic polyphosphate which modulates Lon protease to degrade antitoxins...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27931778/a-magic-spot-in-genome-maintenance
#9
REVIEW
Aviram Rasouly, Bibhusita Pani, Evgeny Nudler
Nucleotide excision repair (NER) is the key DNA repair system that eliminates the majority of DNA helix-distorting lesions. RNA polymerase (RNAP) expedites the recognition of DNA damage by NER components via transcription-coupled DNA repair (TCR). In bacteria, a modified nucleotide ppGpp ('magic spot') is a pleiotropic second messenger that mediates the response to nutrient deficiencies by altering the initiation properties of RNAP. In this review, we discuss newly elucidated roles of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) in transcription elongation that couple this alarmone to DNA damage repair and maintenance...
January 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27915292/the-dual-role-of-dksa-protein-in-the-regulation-of-escherichia-coli-pargx-promoter
#10
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
#11
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
#12
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
#13
André A Pulschen, Diego E Sastre, Federico Machinandiarena, Agostina Crotta Asis, Daniela Albanesi, Diego de Mendoza, Frederico 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 on 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
#14
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
#15
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 roles of several small accessory subunits within the complex have 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...
January 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/27775002/auxotrophy-based-high-throughput-screening-assay-for-the-identification-of-bacillus-subtilis-stringent-response-inhibitors
#16
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
#17
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...
December 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
#18
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
#19
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
#20
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
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