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https://www.readbyqxmd.com/read/28186774/quantitative-map-of-%C3%AE-lactone-induced-virulence-regulation
#1
Joanna Krysiak, Matthias Stahl, Jan Vomacka, Christian Fetzer, Markus Lakemeyer, Anja Fux, Stephan A Sieber
β-Lactones have recently been introduced as the first selective ClpP inhibitors that attenuate virulence of both sensitive Staphylococcus aureus and multiresistant strains (MRSA). Although previous knockout studies showed that ClpP is essential for S. aureus alpha-toxin production, a link between β-lactone inhibition and molecular virulence mechanisms has been lacking so far. We here perform a chemical-proteomic approach to elucidate antivirulence pathways. First, we demonstrate by gel-free activity-based protein profiling that ClpP is the predominant target of β-lactones...
February 10, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28178980/novel-neuro-audiological-findings-and-further-evidence-for-twnk-involvement-in-perrault-syndrome
#2
Monika Ołdak, Dominika Oziębło, Agnieszka Pollak, Iwona Stępniak, Michal Lazniewski, Urszula Lechowicz, Krzysztof Kochanek, Mariusz Furmanek, Grażyna Tacikowska, Dariusz Plewczynski, Tomasz Wolak, Rafał Płoski, Henryk Skarżyński
BACKGROUND: Hearing loss and ovarian dysfunction are key features of Perrault syndrome (PRLTS) but the clinical and pathophysiological features of hearing impairment in PRLTS individuals have not been addressed. Mutations in one of five different genes HSD17B4, HARS2, LARS2, CLPP or TWNK (previous symbol C10orf2) cause the autosomal recessive disorder but they are found only in about half of the patients. METHODS: We report on two siblings with a clinical picture resembling a severe, neurological type of PRLTS...
February 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28178222/complete-chloroplast-genome-of-medicinal-plant-lonicera-japonica-genome-rearrangement-intron-gain-and-loss-and-implications-for-phylogenetic-studies
#3
Liu He, Jun Qian, Xiwen Li, Zhiying Sun, Xiaolan Xu, Shilin Chen
The complete chloroplast (cp) genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions (IRa and IRb), of 23,774 bp each, as well as large (LSC, 88,858 bp) and small (SSC, 18,672 bp) single-copy regions. A total of 129 genes were identified in the cp genome, 16 of which were duplicated within the IR regions. Relative to other plant cp genomes, the L...
February 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28170446/community-level-physiological-profiling-analyses-show-potential-to-identify-the-copiotrophic-bacteria-present-in-soil-environments
#4
Salvador Lladó, Petr Baldrian
Community-level physiological profiling (CLPP) analyses from very diverse environments are frequently used with the aim of characterizing the metabolic versatility of whole environmental bacterial communities. While the limitations of the methodology for the characterization of whole communities are well known, we propose that CLPP combined with high-throughput sequencing and qPCR can be utilized to identify the copiotrophic, fast-growing fraction of the bacterial community of soil environments, where oligotrophic taxa are usually dominant...
2017: PloS One
https://www.readbyqxmd.com/read/28114338/proteolysis-dependent-remodeling-of-the-tubulin-homolog-ftsz-at-the-division-septum-in-escherichia-coli
#5
Marissa G Viola, Christopher J LaBreck, Joseph Conti, Jodi L Camberg
During bacterial cell division a dynamic protein structure called the Z-ring assembles at the septum. The major protein in the Z-ring in Escherichia coli is FtsZ, a tubulin homolog that polymerizes with GTP. FtsZ is degraded by the two-component ATP-dependent protease ClpXP. Two regions of FtsZ, located outside of the polymerization domain in the unstructured linker and at the C-terminus, are important for specific recognition and degradation by ClpXP. We engineered a synthetic substrate containing green fluorescent protein (Gfp) fused to an extended FtsZ C-terminal tail (residues 317-383), including the unstructured linker and the C-terminal conserved region, but not the polymerization domain, and showed that it is sufficient to target a non-native substrate for degradation in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28105941/the-loss-of-photosynthetic-pathways-in-the-plastid-and-nuclear-genomes-of-the-non-photosynthetic-mycoheterotrophic-eudicot-monotropa-hypopitys
#6
Nikolai V Ravin, Eugeny V Gruzdev, Alexey V Beletsky, Alexander M Mazur, Egor B Prokhortchouk, Mikhail A Filyushin, Elena Z Kochieva, Vitaly V Kadnikov, Andrey V Mardanov, Konstantin G Skryabin
BACKGROUND: Chloroplasts of most plants are responsible for photosynthesis and contain a conserved set of about 110 genes that encode components of housekeeping gene expression machinery and photosynthesis-related functions. Heterotrophic plants obtaining nutrients from other organisms and their plastid genomes represent model systems in which to study the effects of relaxed selective pressure on photosynthetic function. The most evident is a reduction in the size and gene content of the plastome, which correlates with the loss of genes encoding photosynthetic machinery which become unnecessary...
November 16, 2016: BMC Plant Biology
https://www.readbyqxmd.com/read/28098783/the-influence-of-the-toxin-antitoxin-mazef-on-growth-and-survival-of-listeria-monocytogenes-under-stress
#7
Thomas D Curtis, Ippei Takeuchi, Lone Gram, Gitte M Knudsen
A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σ(B)). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σ(B) operon in L. monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added...
January 13, 2017: Toxins
https://www.readbyqxmd.com/read/28061786/attenuated-actinobacillus-pleuropneumoniae-double-deletion-mutant-s-8%C3%A2-clpp-apxiic-confers-protection-against-homologous-or-heterologous-strain-challenge
#8
RANDOMIZED CONTROLLED TRIAL
Fang Xie, Gang Li, Long Zhou, Yanhe Zhang, Ning Cui, Siguo Liu, Chunlai Wang
BACKGROUND: Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, which leads to large economic losses to the swine industry worldwide. In this study, S-8△clpP△apxIIC, a double-deletion mutant of A. pleuropneumoniae was constructed, and its safety and protective efficacy were evaluated in pigs. RESULTS: The S-8△clpP△apxIIC mutant exhibited attenuated virulence in a murine (BALB/c) model, and caused no detrimental effects on pigs even at a dose of up to 1...
January 6, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28049149/rela-mutant-enterococcus-faecium-with-multiantibiotic-tolerance-arising-in-an-immunocompromised-host
#9
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/28011364/functionality-of-microbial-communities-in-constructed-wetlands-used-for-pesticide-remediation-influence-of-system-design-and-sampling-strategy
#10
Tao Lv, Pedro N Carvalho, Liang Zhang, Yang Zhang, Mark Button, Carlos A Arias, Kela P Weber, Hans Brix
The objective of this study was to compare the microbial community metabolic function from both unsaturated and saturated constructed wetland mesocosms (CWs) when treating the pesticide tebuconazole. The comparison was performed for both interstitial water and substrate biofilm by community level physiological profiling (CLPP) via BIOLOG™ EcoPlates. For each CW design (saturated or unsaturated), six mesocosms were established including one unplanted and five planted individually with either Juncus effusus, Typha latifolia, Berula erecta, Phragmites australis or Iris pseudacorus...
December 18, 2016: Water Research
https://www.readbyqxmd.com/read/28008780/carnosine-inhibits-the-proliferation-of-human-cervical-gland-carcinoma-cells-through-inhibiting-both-mitochondrial-bioenergetics-and-glycolysis-pathways-and-retarding-cell-cycle-progression
#11
Yun Bao, Saidan Ding, Jiaoyan Cheng, Yuan Liu, Bingyu Wang, Huijuan Xu, Yao Shen, Jianxin Lyu
Carnosine has been demonstrated to play an antitumorigenic role in certain types of cancer. However, its underlying mechanism is unclear. In this study, the roles of carnosine in cell proliferation and its underlying mechanism were investigated in the cultured human cervical gland carcinoma cells HeLa and cervical squamous carcinoma cells SiHa. The results showed that carnosine exerted a significant inhibitory effect on the proliferation of HeLa cells, whereas its inhibitory action on the proliferation of SiHa cells was much weaker...
December 1, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27981232/strain-dependent-recognition-of-a-unique-degradation-motif-by-clpxp-in-streptococcus-mutans
#12
Biswanath Jana, Liang Tao, Indranil Biswas
Streptococcus mutans, a dental pathogen, has a remarkable ability to cope with environmental stresses. Under stress conditions, cytoplasmic proteases play a major role in controlling the stability of regulatory proteins and preventing accumulation of damaged and misfolded proteins. ClpXP, a well-conserved cytoplasmic proteolytic system, is crucial in maintaining cellular homeostasis in bacteria. ClpX is primarily responsible for recognition of substrates and subsequent translocation of unfolded substrates into the ClpP proteolytic compartment for degradation...
November 2016: MSphere
https://www.readbyqxmd.com/read/27966496/recent-excitements-in-protein-nmr-large-proteins-and-biologically-relevant-dynamics
#13
Sai Chaitanya Chiliveri, Mandar V Deshmukh
The advent of Transverse Relaxation Optimized SpectroscopY (TROSY) and perdeuteration allowed biomolecular NMR spectroscopists to overcome the size limitation barrier (approx. 20 kDa) in de novo structure determination of proteins. The utility of these techniques was immediately demonstrated on large proteins and protein complexes (e.g. GroELGroES, ClpP protease, Hsp90-p53, 20S proteasome, etc.). Further, recent methodological developments such as Residual Dipolar Couplings and Paramagnetic Relaxation Enhancement allowed accurate measurement of long-range structural restraints...
December 2016: Journal of Biosciences
https://www.readbyqxmd.com/read/27926857/a-lon-clpp-proteolytic-axis-degrades-complex-i-to-extinguish-ros-production-in-depolarized-mitochondria
#14
Kenneth Robert Pryde, Jan Willem Taanman, Anthony Henry Schapira
Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and in Parkinson's disease (PD) in particular. PINK1 and Parkin gene mutations are causes of autosomal recessive PD, and these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It is widely assumed that impaired mitophagy causes PD, as toxic reactive oxygen species (ROS)-producing mitochondria accumulate and progressively drive neurodegeneration. Instead, we report that a LON-ClpP proteolytic quality control axis extinguishes ROS in depolarized mitochondria by degrading the complex I ROS-generating domain...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27899912/specific-mri-abnormalities-reveal-severe-perrault-syndrome-due-to-clpp-defects
#15
Tom E J Theunissen, Radek Szklarczyk, Mike Gerards, Debby M E I Hellebrekers, Elvira N M Mulder-Den Hartog, Jo Vanoevelen, Rick Kamps, Bart de Koning, S Lane Rutledge, Thomas Schmitt-Mechelke, Carola G M van Berkel, Marjo S van der Knaap, Irenaeus F M de Coo, Hubert J M Smeets
In establishing a genetic diagnosis in heterogeneous neurological disease, clinical characterization and whole exome sequencing (WES) go hand-in-hand. Clinical data are essential, not only to guide WES variant selection and define the clinical severity of a genetic defect but also to identify other patients with defects in the same gene. In an infant patient with sensorineural hearing loss, psychomotor retardation, and epilepsy, WES resulted in identification of a novel homozygous CLPP frameshift mutation (c...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27899793/bacterial-proteases-untapped-antimicrobial-drug-targets
#16
REVIEW
Elizabeth Culp, Gerard D Wright
Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs)...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27865008/biosynthesis-of-the-psychotropic-plant-diterpene-salvinorin-a-discovery-and-characterization-of-the-salvia-divinorum-clerodienyl-diphosphate-synthase
#17
Kyle A Pelot, Rod Mitchell, Moonhyuk Kwon, David M Hagelthorn, Jacob F Wardman, Angela Chiang, Jörg Bohlmann, Dae-Kyun Ro, Philipp Zerbe
Salvia divinorum commonly known as diviner's sage, is an ethnomedicinal plant of the mint family (Lamiaceae). S. divinorum is rich in clerodane-type diterpenoids, which accumulate predominantly in leaf glandular trichomes. The main bioactive metabolite, salvinorin A, is the first non-nitrogenous natural compound known to function as an opioid-receptor agonist, and is undergoing clinical trials for potential use in treating neuropsychiatric diseases and drug addictions. We report here the discovery and functional characterization of two S...
November 19, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27831584/the-development-of-small-molecule-modulators-for-clpp-protease-activity
#18
REVIEW
Fei Ye, Jiahui Li, Cai-Guang Yang
The global spread of antibiotic resistance among important human pathogens emphasizes the need to find new antibacterial drugs with a novel mode of action. The ClpP protease has been shown to demonstrate its pivotal importance to both the survival and the virulence of pathogenic bacteria during host infection. Deregulating ClpP activity either through overactivation or inhibition could lead to antibacterial activity, declaiming the dual molecular mechanism for small-molecule modulation. Recently, natural products acyldepsipeptides (ADEPs) have been identified as a new class of antibiotics that activate ClpP to a dysfunctional state in the absence of cognate ATPases...
December 20, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27802578/open-and-compressed-conformations-of-francisella-tularensis-clpp
#19
Laura Díaz-Sáez, Genady Pankov, William N Hunter
Caseinolytic proteases are large oligomeric assemblies responsible for maintaining protein homeostasis in bacteria and in so doing influence a wide range of biological processes. The functional assembly involves three chaperones together with the oligomeric caseinolytic protease catalytic subunit P (ClpP). This protease represents a potential target for therapeutic intervention in pathogenic bacteria. Here, we detail an efficient protocol for production of recombinant ClpP from Francisella tularensis, and the structural characterization of three crystal forms which grow under similar conditions...
January 2017: Proteins
https://www.readbyqxmd.com/read/27797820/clpp-coordinates-mitoribosomal-assembly-through-the-regulation-of-eral1-levels
#20
Karolina Szczepanowska, Priyanka Maiti, Alexandra Kukat, Eduard Hofsetz, Hendrik Nolte, Katharina Senft, Christina Becker, Benedetta Ruzzenente, Hue-Tran Hornig-Do, Rolf Wibom, Rudolf J Wiesner, Marcus Krüger, Aleksandra Trifunovic
Despite being one of the most studied proteases in bacteria, very little is known about the role of ClpXP in mitochondria. We now present evidence that mammalian CLPP has an essential role in determining the rate of mitochondrial protein synthesis by regulating the level of mitoribosome assembly. Through a proteomic approach and the use of a catalytically inactive CLPP, we produced the first comprehensive list of possible mammalian ClpXP substrates involved in the regulation of mitochondrial translation, oxidative phosphorylation, and a number of metabolic pathways...
December 1, 2016: EMBO Journal
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