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https://www.readbyqxmd.com/read/29148853/multi-stage-subunit-vaccines-against-mycobacterium-tuberculosis-an-alternative-to-the-bcg-vaccine-or-a-bcg-prime-boost
#1
Farzad Khademi, Mohammad Derakhshan, Arshid Yousefi-Avarvand, Mohsen Tafaghodi, Saman Soleimanpour
More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants...
November 17, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29148766/heterodimeric-diterpenoids-isolated-from-euphorbia-ebracteolata-roots-and-their-inhibitory-effects-on-%C3%AE-glucosidase
#2
Yunlong Wei, Chao Wang, Zhongbin Cheng, Xiangge Tian, Jingming Jia, Yonglei Cui, Lei Feng, Chengpeng Sun, Baojing Zhang, Xiaochi Ma
Two heterodimeric diterpenoids (1 and 2) comprising abietane lactone and nor-rosane constituent units were isolated from Euphorbia ebracteolata roots. Compound 1 exhibited a moderate inhibitory effect on α-glucosidase (IC50 = 7.94 μM), with a Ki value of 10.8 μM. In silico molecular docking has been performed to investigate the inhibition mechanism. Compound 2 inhibited the acetyl transfer activity of Mycobacterium tuberculosis GlmU (IC50 = 41.85 μM), which is a novel tuberculosis treatment target.
November 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29148755/novel-anti-tubercular-6-dialkylaminopyrimidine-carboxamides-from-phenotypic-whole-cell-high-throughput-screening-of-a-softfocus-library-structure-activity-relationship-and-target-identification-studies
#3
Colin R Wilson, Richard K Gessner, Atica Moosa, Ronnett Seldon, Digby F Warner, Valerie Mizrahi, Candice Soares de Melo, Sandile B Simelane, Aloysius T Nchinda, Efrem Abay, Dale Taylor, Mathew Njoroge, Christel Brunschwig, Nina Lawrence, Helena I M Boshoff, Clifton E Barry, Frederick A Sirgel, Paul van Helden, C John Harris, Richard Gordon, Sonja Ghidelli-Disse, Hannah Pflaumer, Markus Boesche, Gerard Drewes, Olalla Sanz, Gracia Santos, Maria José Rebollo-Lopez, Beatriz Urones, Carolyn Selenski, Maria Jose Lafuente-Monasterio, Matthew Axtman, Joël Lelièvre, Lluis Ballell, Rudolf Mueller, Leslie J Street, Sandeep R Ghorpade, Kelly Chibale
A BioFocus DPI SoftFocus library of ~35,000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with anti-tubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits which passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization...
November 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29147487/a-study-on-the-immune-response-induced-by-a-dna-vaccine-encoding-mtb32c-hbha-antigen-of-mycobacterium-tuberculosis
#4
Roghayeh Teimourpour, Hadi Peeridogaheh, Amir Teimourpour, Mohsen Arzanlou, Zahra Meshkat
Objectives: Tuberculosis (TB) has still remained a global health issue. One third of the world's population is infected with tuberculosis and the current BCG vaccine has low efficiency; hence, it is necessary to develop a new vaccine against TB. The aim of the current study was to evaluate the efficiency of a novel DNA vaccine encoding Mtb32C-HBHA antigen in inducing specific immune responses against Mycobacterium tuberculosis. Materials and Methods: A DNA plasmid vaccine expressing Mtb32C-HBHA fusion protein was constructed and its ability in protein expression was examined by RT-PCR and Western blot methods...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29146858/whole-genome-shotgun-sequences-of-three-multidrug-resistant-mycobacterium-tuberculosis-strains-isolated-from-morocco
#5
Lamiaa Lahlou, Nadia El Mrimar, Meriem Laamarti, Tarek Alouane, Mohammed A Bendahou, Fatna Bssaibis, Yassine Ben Lahlou, Adil Zegmout, N El Hafidi, Rachid ElJaoudi, Mohammed Frikh, Abdelhay Lemnouar, Mostafa Elouennass, Azeddine Ibrahimi
Tuberculosis is a contagious disease that usually attacks the lungs but sometimes attacks other parts of the body, such as the kidneys, glands, and bones. It is an endemic and major public health problem in Morocco. Tuberculosis is transmitted through the airways via the inhalation of microdroplets containing Mycobacterium tuberculosis We present here the whole-genome shotgun sequences of three multidrug-resistant M. tuberculosis strains isolated from Morocco.
November 16, 2017: Genome Announcements
https://www.readbyqxmd.com/read/29145844/development-and-evaluation-of-an-interferon-gamma-assay-for-the-diagnosis-of-tuberculosis-in-red-deer-experimentally-infected-with-mycobacterium-bovis
#6
María Ángeles Risalde, Jobin Thomas, Iker Sevilla, Miriam Serrano, Jose Antonio Ortíz, Joseba Garrido, Mercedes Domínguez, Lucas Domínguez, Christian Gortázar, Jose Francisco Ruíz-Fons
BACKGROUND: Red deer (Cervus elaphus) is regarded as an epidemiologically relevant host for Mycobacterium bovis (M. bovis) and closely related members of the Mycobacterium tuberculosis complex that cause animal tuberculosis (TB). The standard antemortem screening test for the detection of TB in deer is the intradermal tuberculin skin test, but the detection of interferon-gamma (IFNγ) produced by white blood cells exposed to M. bovis antigens can be used as an alternative or supplemental assay in most TB eradication/control programs...
November 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29145154/a-pipeline-for-proteome-scale-identification-and-studies-on-hormone-sensitive-lipases-in-mycobacterium-tuberculosis
#7
Durairaj Sherlin, Sharmila Anishetty
Hormone sensitive lipases (HSLs) play an important role in the survival of M. tuberculosis during dormancy. They help in the utilization of fatty acids from stored lipids. The objective of the current study was to identify all HSLs from the proteome of M. tuberculosis H37Rv. We have developed a novel HSL identification pipeline, based on amino acid sequence homology, presence of conserved motifs and other sequence features deciphered from known HSL dataset. Through this pipeline, we identified 10 proteins as putative HSLs in M...
November 7, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29144174/secondary-metabolites-from-triclisia-gilletii-de-wild-staner-menispermaceae-with-antimycobacterial-activity-against-mycobacterium-tuberculosis
#8
Eric Robert Tiam, Dominique Serge Ngono Bikobo, Auguste Abouem A Zintchem, Norbert Mbabi Nyemeck, Esther Del Florence Moni Ndedi, Patrick Hervé Betote Diboué, Maximilienne Ascension Nyegue, Alex de Théodore Atchadé, Dieudonné Emmanuel Pegnyemb, Christian G Bochet, Ulrich Koert
Triclisinone (2), a new ochnaflavone derivative, was isolated from the aerial parts of Triclisia gilletii, along with known drypemolundein B (1) and eight other known compounds. The chemical shifts of drypemolundein B (1) have been partially revised based on reinterpretation of NMR spectroscopic data. The eight other secondary metabolites are composed of: (+)-nonacosan-10-ol (3); stigmasterol (4), 3-O-β-D-glucopyranosylsitosterol (5), 3-O-β-D-glucopyranosylstigmasterol (6); oleanic acid (7); myricetin (8), quercetin (9) and 3-methoxyquercetin (10)...
November 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29143876/deregulation-of-genes-associated-with-alternate-drug-resistance-mechanisms-in-mycobacterium-tuberculosis
#9
Kalpana Sriraman, Kayzad Nilgiriwala, Dhananjaya Saranath, Anirvan Chatterjee, Nerges Mistry
Alternate mechanisms of drug resistance involving intrinsic defense pathways play an important role in development of drug resistance. Deregulation of drug efflux, cellular metabolism, and DNA repair have been indicated to have effect on drug tolerance and persistence. Here we chose eight genes from these pathways to investigate their association with development of multidrug resistance (MDR). We generated mono drug resistant and MDR strains of rifampicin and isoniazid and examined the differential expression of genes belonging to efflux, DNA repair and cell wall lipid synthesis pathways...
November 16, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29143466/tuberculosis-serosurveillance-and-management-practices-of-captive-african-elephants-loxodonta-africana-in-the-kavango-zambezi-transfrontier-conservation-area
#10
L E Rosen, T G Hanyire, J Dawson, C M Foggin, A L Michel, K P Huyvaert, M A Miller, F J Olea-Popelka
Transfrontier conservation areas represent an international effort to encourage conservation and sustainable development. Their success faces a number of challenges, including disease management in wildlife, livestock and humans. Tuberculosis (TB) affects humans and a multitude of non-human animal species and is of particular concern in sub-Saharan Africa. The Kavango-Zambezi Transfrontier Conservation Area encompasses five countries, including Zimbabwe, and is home to the largest contiguous population of free-ranging elephants in Africa...
November 16, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29143375/an-immunoinformatics-approach-to-define-t-cell-epitopes-from-polyketide-and-non-ribosomal-peptide-synthesis-proteins-of-mycobacterium-tuberculosis-as-potential-vaccine-candidates
#11
S Dhivya, V Baskar, S R Kumar, R Sathishkumar
The role of polyketide and non-ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty-one proteins from polyketide and non-ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides...
November 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29142889/rapid-detection-of-streptomycin-resistant-mycobacterium-tuberculosis-by-rpsl-restriction-fragment-length-polymorphism
#12
Sediqe Karimi, Hossein Mirhendi, Fatemh Riyahi Zaniani, Soroor Erfani Manesh, Mahshd Salehi, Bahram Nasr Esfahani
Background: Molecular methods for the detection of drug-resistant tuberculosis (DR-TB) are potentially more rapid than conventional culture-based drug susceptibility testing, facilitating the commencement of appropriate treatment for patients with DR-TB. The aim of this study was to evaluate and develop polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays for the detection of mutations within rpsL, and for the determination of streptomycin (STR) resistance in Mycobacterium tuberculosis...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/29142798/verification-of-diagnosis-in-tuberculosis-a-case-report-and-discussion
#13
Amanda M Dave, Abed Adelrahman, Vishist Mehta, Stephen Cavalieri, Renuga Vivekanadan
Tuberculosis (TB), caused by strains of Mycobacterium tuberculosis complex (M. tuberculosis), is a pulmonary infection that is spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosisgreatly jeopardize TB control efforts. We report the case of a previously healthy 43-year-old male, visiting from China, who presented to the emergency department complaining of hemoptysis of 10 days' duration. Cultures were positive for acid fast bacteria and negative for fungi...
September 3, 2017: Curēus
https://www.readbyqxmd.com/read/29142508/proteomic-characterisation-of-bovine-and-avian-purified-protein-derivatives-and-identification-of-specific-antigens-for-serodiagnosis-of-bovine-tuberculosis
#14
José Antonio Infantes-Lorenzo, Inmaculada Moreno, María de Los Ángeles Risalde, Álvaro Roy, Margarita Villar, Beatriz Romero, Nieves Ibarrola, José de la Fuente, Eugenia Puentes, Lucía de Juan, Christian Gortázar, Javier Bezos, Lucas Domínguez, Mercedes Domínguez
Background: Bovine purified protein derivative (bPPD) and avian purified protein derivative (aPPD) are widely used for bovine tuberculosis diagnosis. However, little is known about their qualitative and quantitative characteristics, which makes their standardisation difficult. In addition, bPPD can give false-positive tuberculosis results because of sequence homology between Mycobacterium bovis (M. bovis) and M. avium proteins. Thus, the objective of this study was to carry out a proteomic characterisation of bPPD, aPPD and an immunopurified subcomplex from bPPD called P22 in order to identify proteins contributing to cross-reactivity among these three products in tuberculosis diagnosis...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/29142049/the-occurrence-and-nature-of-double-alleles-in-vntr-patterns-of-more-than-8-000-mycobacterium-tuberculosis-complex-isolates-in-the-netherlands
#15
Rana Jajou, Miranda Kamst, Rianne van Hunen, Carolina Catherina de Zwaan, Arnout Mulder, Philip Supply, Richard Anthony, Wim van der Hoek, Dick van Soolingen
Background: Since 2004, variable number of tandem repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates has been applied on a structural basis in The Netherlands to study the epidemiology of tuberculosis (TB). Although this technique is faster and technically less demanding than the previously used restriction fragment length polymorphism (RFLP) typing, reproducibility remains a concern.Methods/results: In the period 2004 -- 2015, 8,532 isolates were subjected to VNTR typing in The Netherlands, of which 186 (2...
November 15, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29142045/a-rapid-assay-for-detection-of-the-epidemiologically-important-central-asian-russian-strain-of-the-mycobacterium-tuberculosis-beijing-genotype
#16
Igor Mokrousov, Ekaterina Chernyaeva, Anna Vyazovaya, Yuriy Skiba, Natalia Solovieva, Violeta Valcheva, Klavdia Levina, Natalya Malakhova, Wei-Wei Jiao, Lia Lima Gomes, Philip N Suffys, Marge Kütt, Nagima Aitkhozhina, A-Dong Shen, Olga Narvskaya, Viacheslav Zhuravlev
Mycobacterium tuberculosis isolates of the Beijing 94-32-cluster (also named "Central Asian/Russian Beijing strain") constitute an important component of the population structure of the pathogen in the Former Soviet Union (FSU) countries (1-4).….
November 15, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29141986/arfgap1-restricts-mycobacterium-tuberculosis-entry-by-controlling-the-actin-cytoskeleton
#17
Ok-Ryul Song, Christophe J Queval, Raffaella Iantomasi, Vincent Delorme, Sabrina Marion, Romain Veyron-Churlet, Elisabeth Werkmeister, Michka Popoff, Isabelle Ricard, Samuel Jouny, Nathalie Deboosere, Frank Lafont, Alain Baulard, Edouard Yeramian, Laurent Marsollier, Eik Hoffmann, Priscille Brodin
The interaction of Mycobacterium tuberculosis (Mtb) with pulmonary epithelial cells is critical for early stages of bacillus colonization and during the progression of tuberculosis. Entry of Mtb into epithelial cells has been shown to depend on F-actin polymerization, though the molecular mechanisms are still unclear. Here, we demonstrate that mycobacterial uptake into epithelial cells requires rearrangements of the actin cytoskeleton, which are regulated by ADP-ribosylation factor 1 (Arf1) and phospholipase D1 (PLD1), and is dependent on the M3 muscarinic receptor (M3R)...
November 15, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29140933/t-spot-tb%C3%A2-performance-in-routine-pediatric-practice-in-a-low-tb-burden-setting
#18
Anna M Mandalakas, Heather Y Highsmith, Nadine M Harris, Anna Pawlicka, H Lester Kirchner
BACKGROUND: The T-SPOT.TB, an interferon-γ release assay (IGRA), is an indirect test of Mycobacterium tuberculosis infection. Due to sparse and conflicting evidence, IGRA use is limited in young and HIV-infected children. We determined the prevalence of invalid, borderline, positive, and negative results and associations with key demographic variables during routine pediatric use in a TB low-burden setting. METHODS: For pediatric samples received at Oxford Diagnostic Laboratories from 2010-2015, the associations between initial test outcome and demographics were estimated by bivariate analysis and logistic regression...
November 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29140686/the-regulatory-mechanism-of-mycobacterium-tuberculosis-phosphoserine-phosphatase-serb2
#19
Gregory A Grant
Almost all organisms contain the same biosynthetic pathway for the synthesis of l-serine from the glycolytic intermediate, D-3-phosphoglycerate. However, regulation of this pathway varies from organism to organism. Many organisms control the activity of the first enzyme in the pathway, D-3-phosphoglyerate dehydrogenase (PGDH), by feedback inhibition through the interaction of l-serine with the ACT domains within the enzyme. The last enzyme in the pathway, phosphoserine phosphatase (PSP) has also been reported to be inhibited by l-serine...
November 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29138284/rapid-diagnosis-of-pulmonary-tuberculosis-and-detection-of-drug-resistance-by-combined-simultaneous-amplification-testing-and-reverse-dot-blot
#20
Yiwen Chen, Lahong Zhang, Liquan Hong, Xian Luo, Juping Chen, Leiming Tang, Jiahuan Chen, Xia Liu, Zhaojun Chen
AIMS: Making a correct and rapid diagnosis is essential for managing pulmonary tuberculosis (PTB), particularly multidrug-resistant tuberculosis. We aimed to evaluate the efficacy of the combination of simultaneous amplification testing (SAT) and reverse dot blot (RDB) for the rapid detection of Mycobacterium tuberculosis (MTB) and drug-resistant mutants in respiratory samples. METHODS: 225 suspected PTB and 32 non-TB pulmonary disease samples were collected. All sputum samples were sent for acid-fast bacilli smear, SAT, culture and drug susceptibility testing (DST) by the BACTEC(TM) MGIT(TM) 960 system...
November 14, 2017: Journal of Clinical Pathology
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