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https://www.readbyqxmd.com/read/28612721/-addiction-of-toxin-antitoxin-systems-to-a-chaperone-in-mycobacterium-tuberculosis
#1
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
#2
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
#3
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...
May 31, 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
#4
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
#5
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
https://www.readbyqxmd.com/read/28338924/a-nonsynonymous-snp-catalog-of-mycobacterium-tuberculosis-virulence-genes-and-its-use-for-detecting-new-potentially-virulent-sublineages
#6
Natalya E Mikheecheva, Marina V Zaychikova, Alexander V Melerzanov, Valery N Danilenko
Mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an M. tuberculosis classification approach based on functional polymorphisms in virulence genes. An M. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin-antitoxin systems...
April 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28298445/the-structure-and-function-of-mycobacterium-tuberculosis-mazf-mt6-toxin-provide-insights-into-conserved-features-of-mazf-endonucleases
#7
Eric D Hoffer, Stacey J Miles, Christine M Dunham
Toxin-antitoxin systems are ubiquitous in prokaryotic and archaeal genomes and regulate growth in response to stress. Escherichia coli contains at least 36 putative toxin-antitoxin gene pairs, and some pathogens such as Mycobacterium tuberculosis have over 90 toxin-antitoxin operons. E. coli MazF cleaves free mRNA after encountering stress, and nine M. tuberculosis MazF family members cleave mRNA, tRNA, or rRNA. Moreover, M. tuberculosis MazF-mt6 cleaves 23S rRNA Helix 70 to inhibit protein synthesis. The overall tertiary folds of these MazFs are predicted to be similar, and therefore, it is unclear how they recognize structurally distinct RNAs...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28258153/rationalized-design-of-a-mucosal-vaccine-protects-against-mycobacterium-tuberculosis-challenge-in-mice
#8
Mushtaq Ahmed, Hongmei Jiao, Racquel Domingo-Gonzalez, Shibali Das, Kristin L Griffiths, Javier Rangel-Moreno, Uma M Nagarajan, Shabaana A Khader
Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a leading cause of global morbidity and mortality. The only licensed TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), has variable efficacy in protecting against pulmonary TB. Thus, the development of more effective TB vaccines is critical to control the TB epidemic. Specifically, vaccines delivered through the mucosal route are known to induce Th17 responses and provide superior protection against Mtb infection. However, already tested Th17-inducing mucosal adjuvants, such as heat-labile enterotoxins and cholera toxins, are not considered safe for use in humans...
March 3, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28137237/model-systems-for-pulmonary-infectious-diseases-paradigms-of-anthrax-and-tuberculosis
#9
Gunjan Arora, Richa Misra, Andaleeb Sajid
Robert Koch utilized animal model systems to put forward his postulates while discovering the etiological agents of anthrax and tuberculosis, Bacillus anthracis and Mycobacterium tuberculosis, respectively. After more than 130 years, we have achieved limited success towards understanding these two pestilences, which have propagated as scourge against humans. B. anthracis and M. tuberculosis are diverse organisms, which share a common evolutionary path in tropics. They adapt unique strategies to overcome unfavorable conditions and surpass the host defense mechanisms...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28088183/incidence-aetiology-and-outcome-of-community-acquired-acute-kidney-injury-in-medical-admissions-in-malawi
#10
Rhys D R Evans, Ulla Hemmilä, Alison Craik, Mwayi Mtekateka, Fergus Hamilton, Zuze Kawale, Christopher J Kirwan, Hamish Dobbie, Gavin Dreyer
BACKGROUND: Epidemiological data on Acute Kidney Injury (AKI) from low-income countries is sparse. The aim of this study was to establish the incidence, severity, aetiology, and outcomes of community-acquired AKI in Malawi. METHODS: We conducted a prospective observational study of general medical admissions to a tertiary hospital in Blantyre between 27(th) April and 17(th) July 2015. All patients were screened on admission with a serum creatinine; those with creatinine above laboratory reference range were managed by the nephrology team...
January 14, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/27939941/the-toxin-antitoxin-system-dartg-catalyzes-reversible-adp-ribosylation-of-dna
#11
Gytis Jankevicius, Antonio Ariza, Marijan Ahel, Ivan Ahel
The discovery and study of toxin-antitoxin (TA) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. Here we identify and characterize a TA system found in various bacteria, including the global pathogen Mycobacterium tuberculosis. The toxin of the system (DarT) is a domain of unknown function (DUF) 4433, and the antitoxin (DarG) a macrodomain protein...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27936238/trehalose-6-phosphate-mediated-toxicity-determines-essentiality-of-otsb2-in-mycobacterium-tuberculosis-in-vitro-and-in-mice
#12
Jan Korte, Marina Alber, Carolina M Trujillo, Karl Syson, Hendrik Koliwer-Brandl, René Deenen, Karl Köhrer, Michael A DeJesus, Travis Hartman, William R Jacobs, Stephen Bornemann, Thomas R Ioerger, Sabine Ehrt, Rainer Kalscheuer
Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27917833/crystal-structure-of-the-toxin-msmeg_6760-the-structural-homolog-of-mycobacterium-tuberculosis-rv2035-a-novel-type-ii-toxin-involved-in-the-hypoxic-response
#13
R Alexandra Bajaj, Mark A Arbing, Annie Shin, Duilio Cascio, Linda Miallau
The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin-antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate-latch mechanism...
December 1, 2016: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/27891500/interspecies-communication-between-pathogens-and-immune-cells-via-bacterial-membrane-vesicles
#14
Katerina S Jurkoshek, Ying Wang, Jaffre J Athman, Marian R Barton, Pamela A Wearsch
The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27827369/chaperone-addiction-of-toxin-antitoxin-systems
#15
Patricia Bordes, Ambre Julie Sala, Sara Ayala, Pauline Texier, Nawel Slama, Anne-Marie Cirinesi, Valérie Guillet, Lionel Mourey, Pierre Genevaux
Bacterial toxin-antitoxin (TA) systems, in which a labile antitoxin binds and inhibits the toxin, can promote adaptation and persistence by modulating bacterial growth in response to stress. Some atypical TA systems, known as tripartite toxin-antitoxin-chaperone (TAC) modules, include a molecular chaperone that facilitates folding and protects the antitoxin from degradation. Here we use a TAC module from Mycobacterium tuberculosis as a model to investigate the molecular mechanisms by which classical TAs can become 'chaperone-addicted'...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27723728/the-type-vii-secretion-system-of-staphylococcus-aureus-secretes-a-nuclease-toxin-that-targets-competitor-bacteria
#16
Zhenping Cao, M Guillermina Casabona, Holger Kneuper, James D Chalmers, Tracy Palmer
The type VII protein secretion system (T7SS) plays a critical role in the virulence of human pathogens including Mycobacterium tuberculosis and Staphylococcus aureus. Here, we report that the S. aureus T7SS secretes a large nuclease toxin, EsaD. The toxic activity of EsaD is neutralized during its biosynthesis through complex formation with an antitoxin, EsaG, which binds to its C-terminal nuclease domain. The secretion of EsaD is dependent on a further accessory protein, EsaE, that does not interact with the nuclease domain, but instead binds to the EsaD N-terminal region...
October 10, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27696234/toxin-a-negative-toxin-b-positive-ribotype-017-clostridium-difficile-is-the-dominant-strain-type-in-patients-with-diarrhoea-attending-tuberculosis-hospitals-in-cape-town-south-africa
#17
B Kullin, J Wojno, V Abratt, S J Reid
The molecular epidemiology of C. difficile strains causing disease in South Africa is currently unknown. Previously, multidrug resistant ribotype (RT)017 strains were those most commonly isolated from patients with diarrhoea attending Groote Schuur Hospital in Cape Town, South Africa. This larger study aimed to investigate the molecular epidemiology and antibiotic susceptibility profiles of C. difficile strains in the greater Cape Town and regional areas. C. difficile strains were isolated from patients with diarrhoea attending hospitals in the Western Cape region of South Africa that tested positive using the GeneXpert CDiff diagnostic test...
January 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27676811/assessment-of-pain-during-the-injection-of-the-botulinum-toxin-physical-medicine-and-rehabilitation-experience
#18
Samira Lahrabli, Herman Azanmasso, Fatima Lmidmani, Abdellatif El Fatimi
OBJECTIVE: Intramuscular injection of botulinum toxin can be painful for some patients. This may be due either to a broken skin, stimulation for locating, or injecting the product. The objective of this study was to see the clinical impact of pain on injection. MATERIAL/PATIENTS AND METHODS: Retrospective study of 15 patients (6 M/9 W), average age was 31 years (11-75 years). The patients had spasticity of MS in 40% and a MI spasticity in 60%. The treatment was basic Dysport...
September 2016: Annals of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/27645247/moxifloxacin-is-a-potent-in-vitro-inhibitor-of-oct-and-mate-mediated-transport-of-metformin-and-ethambutol
#19
Lindsey H M Te Brake, Jeroen J M W van den Heuvel, Aaron O Buaben, Reinout van Crevel, Albert Bilos, Frans G Russel, Rob E Aarnoutse, Jan B Koenderink
It is largely unknown if simultaneous administration of tuberculosis (TB) drugs and metformin leads to drug-drug interactions (DDIs). Disposition of metformin is determined by organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs). Thus, any DDIs would primarily be mediated via these transporters. This study aimed to assess the in vitro inhibitory effects of TB drugs (rifampin, isoniazid, pyrazinamide, ethambutol, amikacin, moxifloxacin, and linezolid) on metformin transport and whether TB drugs are also substrates themselves of OCTs and MATEs...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27599842/vapcs-of-mycobacterium-tuberculosis-cleave-rnas-essential-for-translation
#20
Kristoffer Winther, Jai J Tree, David Tollervey, Kenn Gerdes
The major human pathogen Mycobacterium tuberculosis can survive in the host organism for decades without causing symptoms. A large cohort of Toxin-Antitoxin (TA) modules contribute to this persistence. Of these, 48 TA modules belong to the vapBC (virulence associated protein) gene family. VapC toxins are PIN domain endonucleases that, in enterobacteria, inhibit translation by site-specific cleavage of initiator tRNA. In contrast, VapC20 of M. tuberculosis inhibits translation by site-specific cleavage of the universally conserved Sarcin-Ricin loop (SRL) in 23S rRNA...
November 16, 2016: Nucleic Acids Research
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