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https://www.readbyqxmd.com/read/28453555/multi-subunit-bcg-booster-vaccine-gamtbvac-assessment-of-immunogenicity-and-protective-efficacy-in-murine-and-guinea-pig-tb-models
#1
A P Tkachuk, V A Gushchin, V D Potapov, A V Demidenko, V G Lunin, A L Gintsburg
New innovative vaccines are highly needed to combat the global threat posed by tuberculosis. Efficient components-antigens and adjuvants-are crucial for development of modern recombinant TB vaccines. This study describes a new vaccine (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6-CFP10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in murine and guinea pig TB models...
2017: PloS One
https://www.readbyqxmd.com/read/28449243/pathologic-features-of-mycobacteriosis-in-naturally-infected-syngnathidae-and-novel-transcriptome-assembly-in-association-with-disease
#2
S B Fogelson, M D Fast, J Leary, A C Camus
Syngnathidae (seahorses, seadragons and pipefish) suffer significant losses from non-tuberculous mycobacteria. However, they produce markedly different lesions in response to the disease compared to other teleost species, notably infrequent granuloma formation. This study evaluated 270 syngnathid fish, from which 92 were diagnosed with mycobacteriosis by histopathology, culture or both. Microscopic lesions variably consisted of random foci of coagulative necrosis in multiple organs, containing high numbers of free bacteria and large aggregates or sheets of macrophages with cytoplasm laden with acid-fast bacilli...
April 27, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28448585/impact-of-temperature-and-soil-type-on-mycobacterium-bovis-survival-in-the-environment
#3
Elodie Barbier, Murielle Rochelet, Laurent Gal, Maria Laura Boschiroli, Alain Hartmann
Mycobacterium bovis, the causative agent of the bovine tuberculosis (bTB), mainly affects cattle, its natural reservoir, but also a wide range of domestic and wild mammals. Besides direct transmission via contaminated aerosols, indirect transmission of the M. bovis between wildlife and livestock might occur by inhalation or ingestion of environmental substrates contaminated through infected animal shedding. We monitored the survival of M. bovis in two soil samples chosen for their contrasted physical and-chemical properties (i...
2017: PloS One
https://www.readbyqxmd.com/read/28448028/system-for-efficacy-and-cytotoxicity-screening-of-inhibitors-targeting-intracellular-mycobacterium-tuberculosis
#4
Xingji Zheng, Yossef Av-Gay
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a leading cause of morbidity and mortality worldwide. With the increased spread of multi drug-resistant TB (MDR-TB), there is a real urgency to develop new therapeutic strategies against M. tuberculosis infections. Traditionally, compounds are evaluated based on their antibacterial activity under in vitro growth conditions in broth; however, results are often misleading for intracellular pathogens like M. tuberculosis since in-broth phenotypic screening conditions are significantly different from the actual disease conditions within the human body...
April 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447869/mitigation-of-discordant-rifampicin-susceptibility-results-obtained-by-xpert-mycobacterium-tuberculosis-rifampicin-and-mycobacterium-growth-indicator-tube
#5
Elmira Gurbanova, Rafail Mehdiyev, Kai Blondal, Rasim Tahirli, Fuad Mirzayev, Doris Hillemann, Asker Ismayilov, Alan Altraja
BACKGROUND: Simultaneous use of genotypic and phenotypic diagnostic tools for detection of rifampicin (RIF) susceptibility may yield discrepant results. OBJECTIVE: To measure the discordance between the RIF-susceptibility results by Xpert MTB/RIF and Mycobacterium Growth Indicator Tube (MGIT), to evaluate if application of both tests to the same sample affects the discrepancy, and to evaluate treatment outcome in patients with the discordant strains. DESIGN: Sputa from patients with tuberculosis managed in the penitentiary system of Azerbaijan during 2011-2015 were examined for RIF susceptibility using Xpert MTB/RIF and MGIT...
April 27, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28447476/mtbvac-from-discovery-to-clinical-trials-in-tuberculosis-endemic-countries
#6
Dessislava Marinova, Jesus Gonzalo-Asensio, Nacho Aguilo, Carlos Martin
BCG remains the only vaccine against tuberculosis (TB) in use today and despite its impressive global coverage, the nature of BCG protection against the pulmonary forms of TB remains subject to ongoing debate. Because of the limitations of BCG, novel TB vaccine candidates have been developed and several have reached the clinical pipeline. One of these candidates is MTBVAC, the first and only TB vaccine in the clinical pipeline to date based on live-attenuated Mycobacterium tuberculosis that has successfully entered clinical evaluation, a historic milestone in human vaccinology...
April 27, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28447386/unraveling-the-pleiotropic-role-of-the-mceg-atpase-in-mycobacterium-smegmatis
#7
Julia García-Fernández, Kadamba Papavinasasundaram, Beatriz Galán, Christopher M Sassetti, José L García
The Mce systems are complex ABC transporters that are encoded by different numbers of homologous operons in Actinobacteria. While the four Mce systems of Mycobacterium tuberculosis are all energized by a single ATPase, MceG, each system appears to import different fatty acids or sterols. To explore if this behavior can be extended to saprophytic mycobacteria, whose more complex genomes encode more Mce systems, we have identified and characterized the MceG ortholog of Mycobacterium smegmatis. This bacterium relies on MceG to energize its 6 Mce systems that contribute to a variety of cellular functions including sterol uptake and cell envelope maintenance...
April 26, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28446902/modulation-of-macrophage-responses-by-cmx-a-fusion-protein-composed-of-ag85c-mpt51-and-hspx-from-mycobacterium-tuberculosis
#8
Adeliane C da Costa, Danilo P de Resende, Bruno de P O Santos, Karina F Zoccal, Lúcia H Faccioli, André Kipnis, Ana P Junqueira-Kipnis
Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that Mycobacterium smegmatis expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28446822/anti-mycobacterium-activity-of-microbial-peptides-in-a-silkworm-infection-model-with-mycobacterium-smegmatis
#9
Akiho Yagi, Ryuji Uchida, Hiroshi Hamamoto, Kazuhisa Sekimizu, Ken-Ichi Kimura, Hiroshi Tomoda
An in vivo-mimic silkworm infection model with Mycobacterium smegmatis was established. When silkworms were raised at 37 °C following an injection of M. smegmatis cells (1.25 × 10(7) CFU larva(-1) g(-1)) into the silkworm hemolymph, they died within 48 h. Under these conditions, four microbial peptides with anti-M. smegmatis activity, lariatin A, calpinactam, lysocin E and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active against Mycobacterium tuberculosis...
May 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28446777/structural-investigations-on-orotate-phosphoribosyltransferase-from-mycobacterium-tuberculosis-a-key-enzyme-of-the-de-novo-pyrimidine-biosynthesis
#10
Stefano Donini, Davide M Ferraris, Riccardo Miggiano, Alberto Massarotti, Menico Rizzi
The Mycobacterium tuberculosis orotate phosphoribosyltransferase (MtOPRT) catalyses the conversion of α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and orotate (OA) in pyrophosphate and orotidine 5'-monophosphate (OMP), in presence of Mg(2+). This enzyme is the only responsible for the synthesis of orotidine 5'-monophosphate, a key precursor in the de novo pyrimidine biosynthesis pathway, making MtOPRT an attractive drug target for the development of antitubercular agents. We report the crystal structures of MtOPRT in complex with PRPP (2...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446771/monitoring-global-protein-thiol-oxidation-and-protein-s-mycothiolation-in-mycobacterium-smegmatis-under-hypochlorite-stress
#11
Melanie Hillion, Jörg Bernhardt, Tobias Busche, Martina Rossius, Sandra Maaß, Dörte Becher, Mamta Rawat, Markus Wirtz, Rüdiger Hell, Christian Rückert, Jörn Kalinowski, Haike Antelmann
Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes. Here, we used shotgun proteomics, OxICAT and RNA-seq transcriptomics to analyse protein S-mycothiolation, reversible thiol-oxidations and their impact on gene expression in Mycobacterium smegmatis under hypochlorite stress. In total, 58 S-mycothiolated proteins were identified under NaOCl stress that are involved in energy metabolism, fatty acid and mycolic acid biosynthesis, protein translation, redox regulation and detoxification...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446574/the-use-of-genexpert-remnants-for-drug-resistance-profiling-and-molecular-epidemiology-of-tuberculosis-in-libreville-gabon
#12
Amel Kévin Alame-Emane, Catherine Pierre-Audigier, Oriane Cordelia Aboumegone-Biyogo, Amandine Nzoghe-Mveang, Véronique Cadet-Daniel, Christophe Sola, Joël Fleury Djoba-Siawaya, Brigitte Gicquel, Howard E Takiff
Multidrug (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis are major problems in global health. The GeneXpertMTB/RIF (Xpert) rapidly detects resistance to rifampicin (RIF-R), but detection of the additional resistance that defines MDR and XDR-TB, and for molecular epidemiology, specimen cultures and biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for Xpert could be used directly to find mutations associated with drug resistance and for molecular epidemiology, and thus provide a precise characterization of MDR-TB cases in countries lacking BSL3 facilities for M...
April 26, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28446563/nontuberculous-mycobacterial-pulmonary-disease-an-increasing-burden-with-substantial-costs
#13
EDITORIAL
D Rebecca Prevots, Robert Loddenkemper, Giovanni Sotgiu, Giovanni Battista Migliori
No abstract text is available yet for this article.
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28446559/burden-of-non-tuberculous-mycobacterial-pulmonary-disease-in-germany
#14
Roland Diel, Josephine Jacob, Niklas Lampenius, Michael Loebinger, Albert Nienhaus, Klaus F Rabe, Felix C Ringshausen
The objective of this study was to estimate the burden of disease in incident patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD).A sample of 7 073 357 anonymised persons covered by German public statutory health insurances was used to identify patients with NTM-PD. In total, 125 patients with newly diagnosed NTM-PD in 2010 and 2011 were matched with 1250 control patients by age, sex and Charlson Comorbidity Index, and followed for 39 months.The incidence rate for NTM-PD was 2.6 per 100 000 insured persons (95% CI 2...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28444886/detection-of-mycobacterium-avium-subsp-paratuberculosis-in-non-human-primates
#15
Kim Fechner, Kerstin Mätz-Rensing, Karen Lampe, Franz-Josef Kaup, Claus-Peter Czerny, Jenny Schäfer
BACKGROUND: Due to a sporadic occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in non-human primates (NHP), the susceptibility of different NHP to MAP should be investigated. METHODS: Fecal and tissue samples (ileum, ileocecal lymph node, bone marrow) of 20 animals (seven species) were analyzed by IS900-based PCRs and sequenced. Samples of MAP PCR positive NHP were further cultivated. RESULTS: MAP DNA was detectable in two animals; the ileum of a cottontop tamarin and the bone marrow of a common marmoset...
April 26, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28443511/current-approaches-and-future-prospects-of-nanomedicines-in-tuberculosis-therapy
#16
Md Tanwir Athar, Zabih Ullah
Tuberculosis (TB), which is caused by the Mycobacterium tuberculosis, is a serious threat and one of the major health problems worldwide. In recent years, an estimated of 9.6 million TB cases occurred and 1.5 million death occurred due to TB worldwide. The present review is an attempt to introduce this disease focusing on the pathophysiology of the disease, the current approachesand the related patents for treatment and the future planningfor combating this disease.
April 25, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28443247/evaluation-of-a-new-ifn-%C3%AE-release-assay-for-rapid-diagnosis-of-active-tuberculosis-in-a-high-incidence-setting
#17
Gen Li, Feng Li, Hui-Min Zhao, Han-Li Wen, Hai-Cong Li, Chun-Ling Li, Ping Ji, Peng Xu, Kang Wu, Zhi-Dong Hu, Shui-Hua Lu, Douglas B Lowrie, Jian-Xin Lv, Xiao-Yong Fan
Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of Mycobacterium tuberculosis (Mtb) infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. TB assay containing Mtb-specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high cost is one of the restricting factors against its clinical application in the developing countries...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28443219/estimating-tuberculin-skin-test-reactions-among-children-and-teenagers-who-received-the-bacillus-calmette-guerin-vaccination-at-birth-a-meta-analysis
#18
Mohammad Sadegh Rezai, Siavosh Abedi, Mahdi Afshari, Mahmood Moosazadeh
OBJECTIVES: Tuberculin skin reaction size is one indicator of bacillus Calmette-Guérin (BCG) vaccine efficacy and a way to diagnose latent infection. Several primary studies have examined this issue. Combining the results of these studies using a meta-analysis will provide reliable evidence regarding this indicator for policymakers. This study aimed to estimate the total frequency of different tuberculin skin test reactions among Iranian children and teenagers who received the BCG vaccination at birth...
February 2017: Osong Public Health and Research Perspectives
https://www.readbyqxmd.com/read/28442758/an-amidase_3-domain-containing-n-acetylmuramyl-l-alanine-amidase-is-required-for-mycobacterial-cell-division
#19
Sibusiso Senzani, Dong Li, Ashima Bhaskar, Christopher Ealand, James Chang, Binayak Rimal, Chengyin Liu, Sung Joon Kim, Neeraj Dhar, Bavesh Kana
Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell division. We demonstrated that deletion of MSMEG_6281 (Ami1) in Mycobacterium smegmatis resulted in the formation of cellular chains, illustrative of cells that were unable to complete division. Suprisingly, viability in the Δami1 mutant was maintained through atypical lateral branching, the products of which proceeded to form viable daughter cells...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442755/global-and-local-environmental-changes-as-drivers-of-buruli-ulcer-emergence
#20
REVIEW
Marine Combe, Camilla Jensen Velvin, Aaron Morris, Andres Garchitorena, Kevin Carolan, Daniel Sanhueza, Benjamin Roche, Pierre Couppié, Jean-François Guégan, Rodolphe Elie Gozlan
Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways...
April 26, 2017: Emerging Microbes & Infections
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