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https://www.readbyqxmd.com/read/29225431/insights-from-the-protein-protein-interaction-network-analysis-of-mycobacterium-tuberculosis-toxin-antitoxin-systems
#1
Zoozeal Thakur, Renu Dharra, Vandana Saini, Ajit Kumar, Promod K Mehta
Protein-protein interaction (PPI) network analysis is a powerful strategy to understand M. tuberculosis (Mtb) system level physiology in the identification of hub proteins. In the present study, the PPI network of 79 Mtb toxin-antitoxin (TA) systems comprising of 167 nodes and 234 edges was investigated. The topological properties of PPI network were examined by 'Network analyzer' a cytoscape plugin app and STRING database. The key enriched biological processes and the molecular functions of Mtb TA systems were analyzed by STRING...
2017: Bioinformation
https://www.readbyqxmd.com/read/29182512/global-mapping-of-mtra-binding-sites-links-mtra-to-regulation-of-its-targets-in-mycobacterium-tuberculosis
#2
Ayan Chatterjee, Arun Kumar Sharma, Amar Chandra Mahatha, Srijon Kaushik Banerjee, Manish Kumar, Sudipto Saha, Joyoti Basu, Manikuntala Kundu
Mycobacterium tuberculosis employs two-component systems (TCSs) for survival within its host. The TCS MtrAB is conserved among mycobacteria. The response regulator MtrA is essential in M. tuberculosis. The genome-wide chromatin immunoprecipitation (ChIP) sequencing performed in this study suggested that MtrA binds upstream of at least 45 genes of M. tuberculosis, including those involved in cell wall remodelling, stress responses, persistence and regulation of transcription. It binds to the promoter regions and regulates the peptidoglycan hydrolases rpfA and rpfC, which are required for resuscitation from dormancy...
November 28, 2017: Microbiology
https://www.readbyqxmd.com/read/29166305/botulinum-toxin-therapy-is-syringe-type-related-to-cost-effectiveness
#3
Mark Anthony Foglietti, Lauren Wright, Alanna Foglietti-Fostyk
INTRODUCTION: Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference...
November 21, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29114057/directed-evolution-of-secb-chaperones-toward-toxin-antitoxin-systems
#4
Ambre Julie Sala, Patricia Bordes, Sara Ayala, Nawel Slama, Samuel Tranier, Michèle Coddeville, Anne-Marie Cirinesi, Marie-Pierre Castanié-Cornet, Lionel Mourey, Pierre Genevaux
SecB chaperones assist protein export in bacteria. However, certain SecB family members have diverged to become specialized toward the control of toxin-antitoxin (TA) systems known to promote bacterial adaptation to stress and persistence. In such tripartite TA-chaperone (TAC) systems, the chaperone was shown to assist folding and to prevent degradation of its cognate antitoxin, thus facilitating inhibition of the toxin. Here, we used both the export chaperone SecB of Escherichia coli and the tripartite TAC system of Mycobacterium tuberculosis as a model to investigate how generic chaperones can specialize toward the control of TA systems...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29089144/adenoviral-vector-mediated-gm-csf-gene-transfer-improves-anti-mycobacterial-immunity-in-mice-role-of-regulatory-t-cells
#5
Alena Singpiel, Julia Kramer, Regina Maus, Jennifer Stolper, Lara Friederike Bittersohl, Jack Gauldie, Martin Kolb, Tobias Welte, Tim Sparwasser, Ulrich A Maus
Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγ(pos) T cells and particularly regulatory T cells (Tregs)...
October 26, 2017: Immunobiology
https://www.readbyqxmd.com/read/29066303/computational-insights-into-promoter-architecture-of-toxin-antitoxin-systems-of-mycobacterium-tuberculosis
#6
Zoozeal Thakur, Vandana Saini, Preeti Arya, Ajit Kumar, Promod K Mehta
Toxin-antitoxin (TA) systems are two component genetic modules widespread in many bacterial genomes, including Mycobacterium tuberculosis (Mtb). The TA systems play a significant role in biofilm formation, antibiotic tolerance and persistence of pathogen inside the host cells. Deciphering regulatory motifs of Mtb TA systems is the first essential step to understand their transcriptional regulation. In this study, in silico approaches, that is, the knowledge based motif discovery and de novo motif discovery were used to identify the regulatory motifs of 79 Mtb TA systems...
October 21, 2017: Gene
https://www.readbyqxmd.com/read/29061131/proguanil-and-cycloguanil-are-organic-cation-transporter-and-multidrug-and-toxin-extrusion-substrates
#7
Maarten van der Velden, Albert Bilos, Jeroen J M W van den Heuvel, Sanna R Rijpma, Evelien G E Hurkmans, Robert W Sauerwein, Frans G M Russel, Jan B Koenderink
BACKGROUND: Malaria, HIV/AIDS, and tuberculosis endemic areas show considerable geographical overlap, leading to incidence of co-infections. This requires treatment with multiple drugs, potentially causing adverse drug-drug interactions (DDIs). As anti-malarials are generally positively charged at physiological pH, they are likely to interact with human organic cation transporters 1 and 2 (OCT1 and OCT2). These transporters are involved in the uptake of drugs into hepatocytes and proximal tubule cells for subsequent metabolic conversion or elimination...
October 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29058054/long-term-high-dose-resveratrol-supplementation-reduces-bone-mass-and-fracture-strength-in-rats
#8
Marie Juul Ornstrup, Annemarie Brüel, Jesper Skovhus Thomsen, Torben Harsløf, Bente Lomholt Langdahl, Steen Bønløkke Pedersen
Resveratrol (RSV) is a natural polyphenolic compound. A recent study suggests a positive effect on BMD in men; however, the underlying changes in microstructure and strength remain unknown. We aimed to investigate the effects of RSV on the skeleton in hindlimb-immobilized and non-immobilized rats. Seventy-two female Wistar rats were divided into six groups. Two baseline (BSL) groups underwent short-term diet intervention for 4 weeks before sacrifice [phytoestrogen-deficient diet (PD) (BSL + PD) or RSV diet (600 mg/kg body weight/day) (BSL + RSV)]...
October 20, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28993337/whole-transcriptome-and-genomic-analysis-of-extensively-drug-resistant-mycobacterium-tuberculosis-clinical-isolates-identifies-downregulation-of-etha-as-a-mechanism-of-ethionamide-resistance
#9
Lynne de Welzen, Vegard Eldholm, Kashmeel Maharaj, Abigail L Manson, Ashlee M Earl, Alexander S Pym
Genetic based drug susceptibility testing has improved the diagnosis of drug-resistant tuberculosis, but is limited by our lack of knowledge of all resistance mechanisms. Next generation sequencing has assisted in identifying the principal genetic mechanisms of resistance for many drugs, but a significant proportion of phenotypic drug resistance is unexplained genetically. Few studies have formally compared the transcriptome of susceptible and resistant M. tuberculosis We carried out comparative whole genome transcriptomics on extensively drug-resistant (XDR) clinical isolates using RNA-sequencing (RNAseq) to find novel transcriptional mediated mechanisms of resistance...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28986943/crystal-structure-of-mycobacterium-tuberculosis-vapc20-toxin-and-its-interactions-with-cognate-antitoxin-vapb20-suggest-a-model-for-toxin-antitoxin-assembly
#10
Amar Deep, Soni Kaundal, Sakshi Agarwal, Ramandeep Singh, Krishan Gopal Thakur
VapBCs, virulence-associated proteins, are the most abundant type II toxin-antitoxin (TA) systems in prokaryotes. Under normal conditions, toxin and antitoxin interact to form a heterooctameric complex, which upon binding to operator sites, inhibits their own expression. Under stress conditions, the VapB antitoxin is degraded by cellular proteases to release a free VapC toxin, which in turn inhibits cell growth mainly by targeting protein translation. However, the intermediate steps involved in the assembly of the heterooctameric complex have not been resolved...
October 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28972145/structural-analyses-of-the-mazef4-toxin-antitoxin-pair-in-mycobacterium-tuberculosis-provide-evidence-for-a-unique-extracellular-death-factor
#11
Do-Hwan Ahn, Ki-Young Lee, Sang Jae Lee, Sung Jean Park, Hye-Jin Yoon, Soon-Jong Kim, Bong-Jin Lee
The bacterial toxin-antitoxin MazEF system in the tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis is activated under unfavorable conditions, including starvation, antibiotic exposure, and oxidative stress. This system contains the ribonucleolytic enzyme MazF and has emerged as a promising drug target for TB treatments targeting the latent stage of M. tuberculosis infection and reportedly mediates a cell death process via a peptide called extracellular death factor (EDF). Although it is well established that the increase in EDFmediated toxicity of MazF drives a cell-killing phenomenon, the molecular details are poorly understood...
October 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28893919/antigen-localisation-influences-the-magnitude-and-kinetics-of-the-endogenous-adaptive-immune-response-to-recombinant-salmonella-vaccines
#12
Yanina R Sevastsyanovich, David R Withers, Claire L Marriott, Faye C Morris, Timothy J Wells, Douglas F Browning, Irene Beriotto, Ewan Ross, Hossam Omar Ali, Catherine A Wardius, Adam F Cunningham, Ian R Henderson, Amanda E Rossiter
The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy to present heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ in where heterologous antigens are expressed and localised within the bacterium and it is unclear how antigen localisation modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in the cell culture supernatant...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28875940/subversion-of-macrophage-functions-by-bacterial-protein-toxins-and-effectors
#13
Muyang Wan, Yan Zhou, Yongqun Zhu
Macrophages represent one of the first lines of host immune defenses against the invasion of pathogenic bacteria. Many receptors, immune signaling pathways and cellular processes in macrophages, including Toll-like receptors, Nod-like receptors, phagocytosis, autophagy and programmed cell death, are involved in combating the infection of bacterial pathogens. For efficient colonization in the host, bacterial pathogens have evolved diverse mechanisms to interfere with macrophage functions to evade host defenses...
September 6, 2017: Current Issues in Molecular Biology
https://www.readbyqxmd.com/read/28724903/co-expression-network-analysis-of-toxin-antitoxin-loci-in-mycobacterium-tuberculosis-reveals-key-modulators-of-cellular-stress
#14
Amita Gupta, Balaji Venkataraman, Madavan Vasudevan, Kiran Gopinath Bankar
Research on toxin-antitoxin loci (TA loci) is gaining impetus due to their ubiquitous presence in bacterial genomes and their observed roles in stress survival, persistence and drug tolerance. The present study investigates the expression profile of all the seventy-nine TA loci found in Mycobacterium tuberculosis. The bacterium was subjected to multiple stress conditions to identify key players of cellular stress response and elucidate a TA-coexpression network. This study provides direct experimental evidence for transcriptional activation of each of the seventy-nine TA loci following mycobacterial exposure to growth-limiting environments clearly establishing TA loci as stress-responsive modules in M...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723479/infectious-complications-of-circumcision-and-their-prevention
#15
REVIEW
Itzhak Brook
CONTEXT: A growing body of evidence supports the health benefits of circumcision, but the occurrence of infectious complications is of concern. OBJECTIVE: To review literature presenting past data and studies of infectious complications of circumcision and their prevention. EVIDENCE ACQUISITION: A literature search was conducted of the Cochrane Library, Embase, Turning Research into Practice, PubMed, and Medline databases from their inception through June 25, 2015...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28612721/-addiction-of-toxin-antitoxin-systems-to-a-chaperone-in-mycobacterium-tuberculosis
#16
Patricia Bordes, Pierre Genevaux
No abstract text is available yet for this article.
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28579801/meat-intake-and-the-dose-of-vitamin-b3-nicotinamide-cause-of-the-causes-of-disease-transitions-health-divides-and-health-futures
#17
REVIEW
Lisa J Hill, Adrian C Williams
Meat and vitamin B3 - nicotinamide - intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by 'welcoming' gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B3 deficiency may now be common among the poor billions on a low-meat diet...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28575388/functional-details-of-the-mycobacterium-tuberculosis-vapbc26-toxin-antitoxin-system-based-on-a-structural-study-insights-into-unique-binding-and-antibiotic-peptides
#18
Sung-Min Kang, Do-Hee Kim, Ki-Young Lee, Sung Jean Park, Hye-Jin Yoon, Sang Jae Lee, Hookang Im, Bong-Jin Lee
Toxin-antitoxin (TA) systems are essential for bacterial persistence under stressful conditions. In particular, Mycobacterium tuberculosis express VapBC TA genes that encode the stable VapC toxin and the labile VapB antitoxin. Under normal conditions, these proteins interact to form a non-toxic TA complex, but the toxin is activated by release from the antitoxin in response to unfavorable conditions. Here, we present the crystal structure of the M. tuberculosis VapBC26 complex and show that the VapC26 toxin contains a pilus retraction protein (PilT) N-terminal (PIN) domain that is essential for ribonuclease activity and that, the VapB26 antitoxin folds into a ribbon-helix-helix DNA-binding motif at the N-terminus...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28363041/decline-of-game-birds-phasianus-colchicus-and-perdix-perdix-in-bavaria-a-survey-on-pathogenic-bacteria-parasites-pesticide-residues-and-influence-of-set-aside-land-and-maize-cultivation
#19
Anna Schmitz, Franz Kronthaler, Katrin Stein, Monika Rinder, Rüdiger Korbel
Due to a Europe-wide decline of grey partridge ( Perdix perdix ) and pheasant ( Phasianus colchicus ) populations, this study was conducted focusing on the county of Bavaria, south Germany. The aim was to assess the health status of game birds and identify possible causes of decline. For this purpose 203 pheasants and 11 partridges were examined during the 2011 hunting season. Pathologic examinations were conducted including examinations for parasites and bacteria. Due to public health significance, a screening for Salmonella sp...
March 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28351618/structure-of-the-mazf-mt9-toxin-a-trna-specific-endonuclease-from-mycobacterium-tuberculosis
#20
Ran Chen, Jie Tu, Zhihui Liu, Fanrong Meng, Pinyun Ma, Zhishan Ding, Chengwen Yang, Lei Chen, Xiangyu Deng, Wei Xie
Tuberculosis (TB) is a severe disease caused by Mycobacterium tuberculosis (M. tb) and the well-characterized M. tb MazE/F proteins play important roles in stress adaptation. Recently, the MazF-mt9 toxin has been found to display endonuclease activities towards tRNAs but the mechanism is unknown. We hereby present the crystal structure of apo-MazF-mt9. The enzyme recognizes tRNA(Lys) with a central UUU motif within the anticodon loop, but is insensitive to the sequence context outside of the loop. Based on our crystallographic and biochemical studies, we identified key residues for catalysis and proposed the potential tRNA-binding site...
May 6, 2017: Biochemical and Biophysical Research Communications
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