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Mycobacterium tuberculosis

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https://www.readbyqxmd.com/read/29334710/-a-study-on-genotype-of-271-mycobacterium-tuberculosis-isolates-in-6-prefectures-in-yunnan-province
#1
L Y Chen, X Yang, H H Ru, H J Yang, S Q Yan, L Ma, J O Chen, R Yang, L Xu
Objective: To understand the characteristics of genotypes of Mycobacterium tuberculosis isolates in Yunnan province, and provide the molecular epidemiological evidence for prevention and control of tuberculosis in Yunnan Province. Methods: Mycobacterium Tuberculosis isolates were collected from 6 prefectures of Yunnan province in 2014 and their Genetypes of Mycobacterium tuberculosis isolates were obtained using spoligotyping and multiple locus variable numbers of tandem repeats analysis (MLVA). The results of spoligotyping were entered into the SITVITWEB database to obtain the Spoligotyping International Type (SIT) patterns and the sublineages of MTB isolates...
January 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29334428/development-of-potent-inhibitors-of-the-mycobacterium-tuberculosis-virulence-factor-zmp1-and-evaluation-of-their-effect-on-mycobacterial-survival-inside-macrophages
#2
Marco Paolino, Margherita Brindisi, Alessandra Vallone, Stefania Butini, Giusepp Campiani, Chiara Nannicini, Germano Giuliani, Maurizio Anzini, Stefania Lamponi, Gianluca Giorgi, Diego Sbardella, Davide M Ferraris, Stefano Marini, Massimo Coletta, Ivana Palucci, Mariachiara Minerva, Giovanni Delogu, Ilaria Pepponi, Delia Goletti, Andrea Cappelli, Sandra Gemma, Simone Brogi
The enzyme Zmp1 is a zinc-peptidase having a critical role in M. tuberculosis pathogenicity. Here we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, 1c was the most potent Zmp1 inhibitor known to date, and its binding mode was analysed both through kinetic studies and molecular modelling, identifying critical interactions of 1c with the zinc-ion and residues in the active site. Effect of 1c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M...
January 15, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29334373/prevention-of-tuberculosis-in-rhesus-macaques-by-a-cytomegalovirus-based-vaccine
#3
Scott G Hansen, Daniel E Zak, Guangwu Xu, Julia C Ford, Emily E Marshall, Daniel Malouli, Roxanne M Gilbride, Colette M Hughes, Abigail B Ventura, Emily Ainslie, Kurt T Randall, Andrea N Selseth, Parker Rundstrom, Lauren Herlache, Matthew S Lewis, Haesun Park, Shannon L Planer, John M Turner, Miranda Fischer, Christina Armstrong, Robert C Zweig, Joseph Valvo, Jackie M Braun, Smitha Shankar, Lenette Lu, Andrew W Sylwester, Alfred W Legasse, Martin Messerle, Michael A Jarvis, Lynn M Amon, Alan Aderem, Galit Alter, Dominick J Laddy, Michele Stone, Aurelio Bonavia, Thomas G Evans, Michael K Axthelm, Klaus Früh, Paul T Edlefsen, Louis J Picker
Despite widespread use of the bacille Calmette-Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent (Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)-which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4+ and CD8+ memory T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334314/on-the-intrinsic-constraint-of-bacterial-growth-rate-m-tuberculosis-s-view-of-the-protein-translation-capacity
#4
Manlu Zhu, Xiongfeng Dai
In nature, the maximal growth rates vary widely among different bacteria species. Fast-growing bacteria species such as Escherichia coli can have a shortest generation time of 20 min. Slow-growing bacteria species are perhaps best known for Mycobacterium tuberculosis, a human pathogen with a generation time being no less than 16 h. Despite of the significant progress made on understanding the pathogenesis of M. tuberculosis, we know little on the origin of its intriguingly slow growth. From a global view, the intrinsic constraint of the maximal growth rate of bacteria remains to be a fundamental question in microbiology...
January 15, 2018: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/29333035/the-activity-of-immunoglobulin-y-anti-mycobacterium-tuberculosis-on-proliferation-and-cytokine-expression-of-rat-peripheral-blood-mononuclear-cells
#5
Sri Agus Sudjarwo, Koerniasari Eraiko, Giftania Wardani Sudjarwo, Koerniasari
Objective: It has long been known that chickens, like mammals, are capable of producing antigen-specific immunoglobulin Y (IgY), which functions similar to IgG. The present study was performed to investigate the activity of IgY anti-Mycobacterium tuberculosis on proliferation, interleukin (IL)-2, and interferon (IFN)-γ expression of rat peripheral blood mononuclear cells (PBMCs). Materials and Methods: The activity of IgY anti-M. tuberculosis in different doses (25, 50, and 100 μg/ml) on rat PBMCs proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332658/an-extremely-rare-association-of-sweet-s-syndrome-with-active-pulmonary-tuberculosis
#6
Sandhya Chauhan
Sweet's syndrome is a skin manifestation of various systemic infections, drugs, malignancies and autoimmune disorders. There are very few case reports describing the relationship between Sweet's syndrome and non-tubercular mycobacterium infection. Further development of Sweet's syndrome secondary to mycobacterium tuberculosis (active pulmonary tuberculosis) is extremely uncommon and this is the second well established case reported from India. Here we report a forty eight year old man who presented with multiple erythematous and tender plaques over neck, palms and sides of soles...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29332649/isoniazid-and-rifampicin-heteroresistant-mycobacterium-tuberculosis-isolated-from-tuberculous-meningitis-patients-in-india
#7
Renu Gupta, Rajeev Thakur, Suman Kushwaha, Nupur Jalan, Pumanshi Rawat, Piyush Gupta, Amitesh Aggarwal, Meena Gupta, Vikas Manchanda
BACKGROUND: Heteroresistant Mycobacterium tuberculosis (mixture of susceptible and resistant subpopulations) is thought to be a preliminary stage to full resistance and timely detection, initiation of correct treatment is vital for successful anti tubercular therapy. The aim of this study was to detect multi drug resistant (MDR) and heteroresistant M. tuberculosis with the associated gene mutations from patients of tuberculous meningitis. METHODS: A total of 197 M...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29332642/current-affairs-future-perspectives-of-tuberculosis-and-antitubercular-agents
#8
REVIEW
Jineetkumar Gawad, Chandrakant Bonde
Tuberculosis (TB) is the major threat for humans from past several decades. Even after advent of several antitubercular drugs, researchers are still struggling for the mycobacterial infections in humans are TB and leprosy. Chronic infections caused by Mycobacterium tuberculosis and Mycobacterium leprae. A particular problem with both of these organisms is that they can survive inside macrophages after phagocytosis, unless these cells are activated by cytokines produced by T-lymphocytes, because of this researchers are not yet succeeded in finding effective treatment on TB...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29331879/structural-and-quantum-mechanical-computations-to-elucidate-the-altered-binding-mechanism-of-metal-and-drug-with-pyrazinamidase-from-mycobacterium-tuberculosis-due-to-mutagenicity
#9
Nouman Rasool, Saima Iftikhar, Anam Amir, Waqar Hussain
Pyrazinamide is known to be the most effective treatment against tuberculosis disease and is known to have bacteriostatic action. By targeting the bacterial spores, this drug reduces the chances for the progression of the infection in organisms. In recent years, increased instances of the drug resistance of bacterial strains are reported. Pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug due to mutagenicity across the world. The present study aimed at the quantum mechanistic analysis of mutations in pyrazinamidase to gain insights into the mechanism of this enzyme...
December 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29330673/vacuum-assisted-closure-therapy-of-paradoxical-reaction-in-tuberculous-lymphadenopathy-caused-by-mycobacterium-africanum
#10
H F Geerdes-Fenge, P Pongratz, J Liese, E C Reisinger
A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula...
January 12, 2018: Infection
https://www.readbyqxmd.com/read/29330469/mycobacterium-tuberculosis-exploits-a-molecular-off-switch-of-the-immune-system-for-intracellular-survival
#11
Ulrich von Both, Maurice Berk, Paul-Michael Agapow, Joseph D Wright, Anna Git, Melissa Shea Hamilton, Greg Goldgof, Nazneen Siddiqui, Evangelos Bellos, Victoria J Wright, Lachlan J Coin, Sandra M Newton, Michael Levin
Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330384/detection-of-apparent-cell-free-m-tuberculosis-dna-from-plasma
#12
E S Click, W Murithi, G S Ouma, K McCarthy, M Willby, S Musau, H Alexander, E Pevzner, J Posey, K P Cain
New diagnostics are needed to improve clinicians' ability to detect tuberculosis (TB) disease in key populations such as children and persons living with HIV and to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma is a diagnostic target in new obstetric and oncologic applications, but its utility for diagnosing TB is not known. Here we show that Mycobacterium tuberculosis complex DNA can be detected in plasma of persons with sputum smear-positive TB, even in the absence of mycobacteremia...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329815/exploring-molecular-insights-into-the-interaction-mechanism-of-cholesterol-derivatives-with-the-mce4a-a-combined-spectroscopic-and-molecular-dynamic-simulation-studies
#13
Shagufta Khan, Faez Iqbal Khan, Taj Mohammad, Parvez Khan, Gulam Mustafa Hasan, Kevin A Lobb, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns...
January 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29328655/identification-of-novel-coumestan-derivatives-as-polyketide-synthase-13-inhibitors-against-mycobacterium-tuberculosis
#14
Wei Zhang, Shichun Lun, Shu-Huan Wang, Xingwu Jiang, Fan Yang, Jie Tang, Abigail L Manson, Ashlee M Earl, Hendra Gunosewoyo, William R Bishai, Li-Fang Yu
Inhibition of the mycolic acid pathway has proven a viable strategy in antitubercular drug discovery. The AccA3/AccD4/FadD32/Pks13 complex of Mycobacterium tuberculosis constitutes an essential biosynthetic mechanism for mycolic acids. Small molecules targeting the thioesterase domain of Pks13 have been reported, including a benzofuran-based compound, whose X-ray co-crystal structure has been very recently solved. Its initial inactivity in a serum inhibition titration (SIT) assay led us to further probe other structurally-related benzofurans with the aim to improve their potency and bioavailability...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29326867/cavitary-lung-lesion-suspicious-for-malignancy-reveals-mycobacterium-xenopi
#15
Sumit Fogla, Vaishali M Pansare, Luis G Camero, Uzma Syeda, Naveen Patil, Arun Chaudhury
We report the case of a 68-year-old gentleman who presented with musculoskeletal chest pain which appeared suddenly when he bent over with his dog. The chest pain was localized to the left lower chest and increased with movement and deep breathing. The patient did not complain weight loss, night sweat, fever or chill. He complained of mild cough, with expectoration of whitish mucus. Imaging revealed cavitary chest lesion in the right upper lobe, which was initially suspected to be lung cancer. The patient had a 50-year-old history of smoking 2 packs per day...
2018: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/29326013/a-cluster-of-multidrug-resistant-mycobacterium-tuberculosis-among-patients-arriving-in-europe-from-the-horn-of-africa-a-molecular-epidemiological-study
#16
Timothy M Walker, Matthias Merker, Astrid M Knoblauch, Peter Helbling, Otto D Schoch, Marieke J van der Werf, Katharina Kranzer, Lena Fiebig, Stefan Kröger, Walter Haas, Harald Hoffmann, Alexander Indra, Adrian Egli, Daniela M Cirillo, Jérôme Robert, Thomas R Rogers, Ramona Groenheit, Anne T Mengshoel, Vanessa Mathys, Marjo Haanperä, Dick van Soolingen, Stefan Niemann, Erik C Böttger, Peter M Keller
BACKGROUND: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. METHODS: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis...
January 8, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29325881/rv2204c-rv0753c-and-rv0009-antigens-specific-t-cell-responses-in-latent-and-active-tb-a-flow-cytometry-based-analysis
#17
Balaji Pathakumari, Santhi Devasundaram, Prabhavathi Maddineni, Alamelu Raja
High global prevalence of latent TB infection (LTBI) is a key challenge in distinguishing patients with active pulmonary TB (PTB) from those with LTBI. The functional profile of CD4+ and CD8+ T cell cytokines produced as a response to Mycobacterium tuberculosis antigens vary during the course of tuberculosis (TB) infection. We evaluated antigen-specific CD4+ and CD8+ T cell cytokine response after overnight in vitro stimulation of peripheral blood with mycobacterial antigens ESAT-6, CFP-10, Rv2204c, Rv0753c and Rv0009 by flow cytometry...
December 6, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29325798/evaluation-of-the-performance-of-two-tuberculosis-interferon-gamma-release-assays-igra-elisa-and-t-spot-tb-for-diagnosing-mycobacterium-tuberculosis-infection
#18
Linchuan Wang, Xu-Dong Tian, Yan Yu, Wei Chen
OBJECTIVES: The IGRA-ELISA and T-SPOT.TB are widely used in China. The aim of the study was to evaluate the performance of the two assays in diagnosis Mycobacterium tuberculosis infection. METHODS: Of the 3727 patients in the study, 204 underwent testing using both the T-SPOT.TB and IGRA-ELISA, 1794 were tested using the T-SPOT.TB only, and 1729 were tested using the IGRA-ELISA only. The positive rate and consistency of the two assays were analyzed, and their sensitivity and specificity for diagnosing active tuberculosis were compared...
January 8, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29325545/phthiocerol-dimycocerosates-promote-access-to-the-cytosol-and-intracellular-burden-of-mycobacterium-tuberculosis-in-lymphatic-endothelial-cells
#19
Thomas R Lerner, Christophe J Queval, Antony Fearns, Urska Repnik, Gareth Griffiths, Maximiliano G Gutierrez
BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans...
January 4, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325465/prevalence-of-positive-quantiferon-gold-in-tube-testing-in-hidradenitis-suppurativa
#20
Tina Boortalary, Kanchan Misra, Sean McNish, Derek Jones, Victoria K Shanmugam
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of the apocrine sweat glands. Tumor necrosis factor-alpha (TNF-α) inhibitors are commonly used to treat HS. However, prior to initiating therapy patients must be screened for mycobacterium tuberculosis (mTB) exposure. Several mTB screening tests based on interferon gamma release assays are commercially available, but the performance of these assays in the HS population is unknown. The purpose of this study was to investigate the performance of the QuantiFERON gold in-tube assay (QFT-GIT) in a cohort of patients with Hidradenitis suppurativa (HS)...
January 12, 2018: Journal of Dermatological Treatment
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