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https://www.readbyqxmd.com/read/29330673/vacuum-assisted-closure-therapy-of-paradoxical-reaction-in-tuberculous-lymphadenopathy-caused-by-mycobacterium-africanum
#1
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
#2
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
#3
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
#4
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
#5
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/29325687/clinical-significance-and-epidemiologic-analyses-of-mycobacterium-avium-and-mycobacterium-intracellulare-lung-disease-from-post-marketing-surveillance
#6
Katsuhiro Suzuki, Atsuyuki Kurashima, Kinji Tatsuno, Jun-Ichi Kadota
BACKGROUND: In Japan, nontuberculous mycobacterial lung disease is mostly attributable to Mycobacterium avium complex (MAC), i.e., M. avium or M. intracellulare. However, clinical features of the disease caused by these two pathogens have not been studied sufficiently yet. METHODS: A post-marketing survey of clarithromycin was performed at 130 facilities across Japan. The data on patients with M. avium infection and patients with M. intracellulare infection were selected from this survey for comparison of background variables and clinical features of the two pathogens...
January 2018: Respiratory Investigation
https://www.readbyqxmd.com/read/29325545/phthiocerol-dimycocerosates-promote-access-to-the-cytosol-and-intracellular-burden-of-mycobacterium-tuberculosis-in-lymphatic-endothelial-cells
#7
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/29322461/enhanced-methodologies-for-detecting-phenotypic-resistance-in-mycobacteria
#8
Robert J H Hammond, Vincent O Baron, Sam Lipworth, Stephen H Gillespie
Lipid droplets found in algae and other microscopic organisms have become of interest to many researchers partially because they carry the capacity to produce bio-oil for the mass market. They are of importance in biology and clinical practice because their presence can be a phenotypic marker of an altered metabolism, including reversible resistance to antibiotics, prompting intense research.A useful stain for detecting lipid bodies in the lab is Nile red. It is a dye that exhibits solvatochromism; its absorption band varies in spectral position, shape and intensity with the nature of its solvent environment, it will fluoresce intensely red in polar environment and blue shift with the changing polarity of its solvent...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321691/deciphering-the-nature-of-the-coral-chromera-association
#9
Amin R Mohamed, Vivian R Cumbo, Saki Harii, Chuya Shinzato, Cheong Xin Chan, Mark A Ragan, Nori Satoh, Eldon E Ball, David J Miller
Since the discovery of Chromera velia as a novel coral-associated microalga, this organism has attracted interest because of its unique evolutionary position between the photosynthetic dinoflagellates and the parasitic apicomplexans. The nature of the relationship between Chromera and its coral host is controversial. Is it a mutualism, from which both participants benefit, a parasitic relationship, or a chance association? To better understand the interaction, larvae of the common Indo-Pacific reef-building coral Acropora digitifera were experimentally infected with Chromera, and the impact on the host transcriptome was assessed at 4, 12, and 48 h post-infection using Illumina RNA-Seq technology...
January 10, 2018: ISME Journal
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#10
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29317751/methylation-in-mycobacterium-tuberculosis-is-lineage-specific-with-associated-mutations-present-globally
#11
Jody Phelan, Paola Florez de Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L Bergval, Richard Anthony, Ruth McNerney, Martin Antonio, Isabel Portugal, Miguel Viveiros, Susana Campino, Martin L Hibberd, Taane G Clark
DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311492/innate-immunity-mediated-by-dendritic-cells-macrophages-plays-a-central-role-in-the-early-period-in-tumor-treatment-using-gene-of-mycobacterium-tuberculosis-antigen
#12
Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
By using a complex of DNA, polyethylenimine and chondroitin sulfate, the in vivo transfection of early secretory antigenic target-6 (ESAT-6) gene into tumor cells was found to cause significant suppression of the tumor growth. In order to apply the method in clinical cancer treatment in dogs and cats, mechanisms underlying the suppressive effects were investigated in a tumor-bearing mouse model. The transfection efficiency was only about 10%, but the transfection of ESAT-6 DNA nevertheless induced systemic immune responses against ESAT-6...
January 1, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29310592/characterization-of-non-tuberculous-mycobacterium-from-humans-and-water-in-an-agropastoral-area-in-zambia
#13
Ngula Monde, Musso Munyeme, Adrian Muwonge, John Bwalya Muma, Sydney Malama
BACKGROUND: The non-tuberculous mycobacteria include those mycobacterium species that are not members of the Mycobacterium tuberculosis complex, the causative agent of pulmonary tuberculosis and Mycobacterium leprae. In Zambia, Non-tuberculous Mycobacteria are gaining recognition as pathogens of public health significance. However, there is scanty information on the isolation and speciation of these organisms for better patient management, consequently reducing the burden of these infections...
January 8, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29301937/cyclipostins-and-cyclophostin-analogs-inhibit-the-antigen-85c-from-mycobacterium-tuberculosis-both-in-vitro-and-in-vivo
#14
Albertus Viljoen, Matthias Richard, Phuong Chi Nguyen, Patrick Fourquet, Luc Camoin, Rishi R Paudal, Giri R Gnawali, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan, Mickael Blaise, Laurent Kremer
An increasing prevalence of cases of drug-resistant tuberculosis requires the development of more efficacious chemotherapies. We previously reported the discovery of a new class of Cyclipostins and Cyclophostin (CyC) analogs exhibiting potent activity against Mycobacterium tuberculosis both in vitro and in infected macrophages. Competitive labeling/enrichment assays combined with MS have identified several serine or cysteine enzymes in lipid and cell wall metabolism as putative targets of these CyC compounds...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29281637/cell-envelope-stress-in-mycobacteria-is-regulated-by-the-novel-signal-transduction-atpase-inir-in-response-to-trehalose
#15
Maikel Boot, Vincent J C van Winden, Marion Sparrius, Robert van de Weerd, Alexander Speer, Roy Ummels, Tige Rustad, David R Sherman, Wilbert Bitter
The cell envelope of mycobacteria is a highly unique and complex structure that is functionally equivalent to that of Gram-negative bacteria to protect the bacterial cell. Defects in the integrity or assembly of this cell envelop must be sensed to allow the induction of stress response systems. The promoter that is specifically and most strongly induced upon exposure to ethambutol and isoniazid, first line drugs that affect cell envelope biogenesis, is the iniBAC promoter. In this study, we set out to identify the regulator of the iniBAC operon in Mycobacterium marinum using an unbiased transposon mutagenesis screen in a constitutively iniBAC-expressing mutant background...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29279791/pulmonary-mycobacterium-avium-intracellulare-complex-infection-in-an-infant-a-silent-and-coincidental-finding
#16
Vishal Naik, Pui-Ying Iroh Tam, William Gershan, Andrew A Colin, Nadir Demirel
An 11-month-old healthy infant girl was noted to have left lower lobe (LLL) opacities on chest X-ray (CXR) after developing desaturations during an elective cochlear implant surgery. Repeat CXR 10 days later revealed hyperexpansion of the left lung and persistent LLL opacity. Chest computerized tomography revealed enlarged mediastinal lymph nodes, left mainstem bronchial obstruction, and nodular opacities. Bronchoscopic biopsy of the endobronchial tissue revealed multiple necrotizing granulomas and grew Mycobacterium avium-intracellulare, Streptococcus viridans, and Actinomyces odontolyticus...
December 1, 2017: Pediatric Allergy, Immunology, and Pulmonology
https://www.readbyqxmd.com/read/29276785/mycobacterium-abscessus-disease-in-lung-transplant-recipients-diagnosis-and-management
#17
Satish Chandrashekaran, Patricio Escalante, Cassie C Kennedy
Mycobacterium abscessus complex (MAbsC ) disease in lung transplant recipients is increasingly being recognized as an important cause of graft function decline and suboptimal outcomes. Lung transplant recipients appear to be at the highest risk of MAbsC among solid organ transplant recipients, as they have more intense immunosuppression, and the organisms preferentially inhabit the lungs. MAbsC is the most resistant species of rapidly growing mycobacteria and difficult to treat, causing considerable mortality and morbidity in immunocompetent and immunosuppressed patients...
December 2017: Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
https://www.readbyqxmd.com/read/29275620/direct-detection-of-products-from-s-adenosylmethionine-dependent-enzymes-using-a-competitive-fluorescence-polarization-assay
#18
Michael T Banco, Vidhi Mishra, Samantha C Greeley, Donald R Ronning
S-adenosylmethionine (AdoMet) dependent methyltransferases (MTases) are an essential superfamily of enzymes that catalyze the transfer of a methyl group to several biomolecules. Alterations in the methylation of cellular components crucially impact vital biological processes, making MTases attractive drug targets for treating infectious diseases and diseases caused by overactive human-encoded MTases. Several methods have been developed for monitoring the activity of MTases, but most MTase assays have inherent limitations or are not amenable for high-throughput screening...
December 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29273966/molecular-characterization-of-amic-a-positive-regulator-in-acetamidase-operon-of-mycobacterium-smegmatis
#19
Arunkumar Venkatesan, Kannan Palaniyandi, Sujatha Narayanan
Mycobacterium smegmatis, a rapidly growing non-pathogenic mycobacterium, is currently used as a model organism to study mycobacterial genetics. Acetamidase of M. smegmatis is the highly inducible enzyme of Mycobacteria, which utilizes several amide compounds as sole carbon and nitrogen sources. The acetamidase operon has a complex regulatory mechanism, which involves three regulatory proteins, four promoters, and three operator elements. In our previous study, we showed that over-expression of AmiA leads to a negative regulation of acetamidase by blocking the P2 promoter...
December 22, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29273788/structure-of-a-wbl-protein-and-implications-for-no-sensing-by-m-tuberculosis
#20
Bassam K Kudhair, Andrea M Hounslow, Matthew D Rolfe, Jason C Crack, Debbie M Hunt, Roger S Buxton, Laura J Smith, Nick E Le Brun, Michael P Williamson, Jeffrey Green
Mycobacterium tuberculosis causes pulmonary tuberculosis (TB) and claims ~1.8 million human lives per annum. Host nitric oxide (NO) is important in controlling TB infection. M. tuberculosis WhiB1 is a NO-responsive Wbl protein (actinobacterial iron-sulfur proteins first identified in the 1970s). Until now, the structure of a Wbl protein has not been available. Here a NMR structural model of WhiB1 reveals that Wbl proteins are four-helix bundles with a core of three α-helices held together by a [4Fe-4S] cluster...
December 22, 2017: Nature Communications
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