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https://www.readbyqxmd.com/read/29330469/mycobacterium-tuberculosis-exploits-a-molecular-off-switch-of-the-immune-system-for-intracellular-survival
#1
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/29322466/using-rt-qpcr-for-quantifying-mycobacteria-marinum-from-in%C3%A2-vitro-and-in-vivo-samples
#2
Han Xaio, Stephen H Gillespie
Mycobacterium marinum, the causative agent of fish tuberculosis, is rarely a human pathogen causing a chronic skin infection. It is now wildely used as a model system in animal models, especially in zebra fish model, to study the pathology of tuberculosis and as a means of screening new anti-tuberculosis agent. To facilitate such research, quantifying the viable count of M. marinum bacteria is a crucial step. The main approach used currently is still by counting the number of colony forming units (cfu), a method that has been in place for almost 100 years...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321924/lung-mycobacterium-avium-developed-after-removing-an-acupuncture-needle-from-the-lung
#3
Mikihito Saito, Hajime Kasai, Kengo Shimazu, Takashi Urushibara, Tomohiko Iida, Toshihide Shinozaki
Acupuncture needles can cause non-tuberculosis mycobacteria (NTM) infection on the skin, but there are no reports that acupuncture needles inserted into the lung have caused lung NTM infection. A 63-year-old woman, who underwent removal of a broken acupuncture needle inserted into the lung nine years ago, was admitted with nodules in the right lung. The shadow was positioned where the needle had existed. Partial lung resection of the right lower lobe was performed, and the resected area showed caseous necrosis histopathologically...
January 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/29321721/antigen-85b-peptidomic-analysis-allows-species-specific-mycobacterial-identification
#4
Wei Zhang, Qingbo Shu, Zhen Zhao, Jia Fan, Christopher J Lyon, Adrian M Zelazny, Ye Hu
Background: Nontuberculous mycobacteria (NTM)-mediated infections are a growing cause of worldwide morbidity, but lack of rapid diagnostics for specific NTM species can delay the initiation of appropriate treatment regimens. We thus examined whether mass spectrometry analysis of an abundantly secreted mycobacterial antigen could identify specific NTM species. Methods: We analyzed predicted tryptic peptides of the major mycobacterial antigen Ag85B for their capacity to distinguish Mycobacterium tuberculosis and three NTM species responsible for the majority of pulmonary infections caused by slow-growing mycobacterial species...
2018: Clinical Proteomics
https://www.readbyqxmd.com/read/29319836/tbc-kan-p%C3%A3-visas-med-pcr-%C3%A2-men-bara-i-direktpositiva-luftv%C3%A3-gsprov
#5
Bodil Jönsson, Elisabet Lönnermark, Malin Ridell
TB can be detected with PCR - but only in smear-positive respiratory samples Unnecessary and inappropriate clinical requests represent a great waste of time and money and may also result in false diagnoses. PCR-techniques, such as Cobas TaqMan MTB, are used for rapid detection of tuberculosis (TB).  These assays are only validated for respiratory specimens, but they are commonly requested also for non-respiratory specimens.  These assays perform well in smear-positive respiratory samples, while the sensitivities are quite unsatisfactory for both respiratory and non-respiratory smear-negatives samples...
January 9, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29313233/evaluation-of-the-efficiency-of-lytic-mycobacteriophage-d29-on-the-model-of-m-tuberculosis-infected-macrophage-raw-264-cell-line
#6
M B Lapenkova, N S Smirnova, P N Rutkevich, M A Vladimirsky
Culture of mouse macrophages (RAW 264.7 ATCC strain) in wells of a 6-well plate was infected with M. tuberculosis in proportion of 15 mycobacteria per one macrophage and then treated with a lytic strain of mycobacteriophage D29. Antibacterial efficacy of mycobacteriophages was studied using D29 phage (activity 108 plaque-forming units/ml) previously purified by ion exchange chromatography. After single and double 24-h treatment, the lysed cultures of macrophages were inoculated onto Middlebrook 7H10 agar medium...
January 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29310671/antituberculosis-activity-phytochemical-identification-of-costus-speciosus-j-koenig-sm-cymbopogon-citratus-dc-ex-nees-stapf-and-tabernaemontana-coronaria-l-willd-and-their-effects-on-the-growth-kinetics-and-cellular-integrity-of-mycobacterium-tuberculosis-h37rv
#7
Suriyati Mohamad, Nur Najihah Ismail, Thaigarajan Parumasivam, Pazilah Ibrahim, Hasnah Osman, Habibah A Wahab
BACKGROUND: Costus speciosus, Cymbopogon citratus, and Tabernaemontana coronaria are herbal plants traditionally used as remedies for symptoms of tuberculosis (TB) including cough. The aims of the present study were to evaluate the in vitro anti-TB activity of different solvent partitions of these plants, to identify the phytochemical compounds, and to assess the effects of the most active partitions on the growth kinetics and cellular integrity of the tubercle organism. METHODS: The in vitro anti-TB activity of different solvent partitions of the plant materials was determined against M...
January 8, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29310592/characterization-of-non-tuberculous-mycobacterium-from-humans-and-water-in-an-agropastoral-area-in-zambia
#8
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/29310027/identification-and-development-of-benzoxazole-derivatives-as-novel-bacterial-glutamate-racemase-inhibitors
#9
Prasanthi Malapati, Vagolu Siva Krishna, Radhika Nallangi, Rudraraju Reshma Srilakshmi, Dharmarajan Sriram
In the present study, we attempted to develop novel class of Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose glutamate racemase was selected which racemizes d-glutamate from l-glutamate, a key step in peptidoglycan synthesis. Furthermore, enzyme is neither expressed nor its product, d-glutamate is produced in mammals, and hence inhibiting this enzyme will have no vulnerable effect in host organism...
December 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29301937/cyclipostins-and-cyclophostin-analogs-inhibit-the-antigen-85c-from-mycobacterium-tuberculosis-both-in-vitro-and-in-vivo
#10
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/29286261/molecular-detection-of-mycobacterium-avium-avium-and-mycobacterium-genavense-in-feces-of-free-living-scarlet-macaw-ara-macao-in-costa-rica
#11
Lena C Patiño W, Otto Monge, Gerardo Suzán, Gustavo Gutiérrez-Espeleta, Andrea Chaves
We conducted a study of the two main populations of free-living Scarlet Macaws ( Ara macao) in Costa Rica to detect the causal agents of avian tuberculosis using noninvasive techniques. We analyzed 83 fecal samples collected between February and May 2016 from the central and southern Pacific areas in the country. Using PCR, we first amplified the 16S region of the rRNA, common to all Mycobacterium species. Products from the insertion sequence IS901 and from a 155-base pair (bp) DNA fragment evidenced the presence of both the avian pathogenic Mycobacterium avium subsp...
December 29, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/29281992/rapidly-growing-mycobacterial-infection-a-recognized-cause-of-early-onset-prosthetic-joint-infection
#12
Anupop Jitmuang, Varah Yuenyongviwat, Keerati Charoencholvanich, Methee Chayakulkeeree
BACKGROUND: Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. METHODS: We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29281637/cell-envelope-stress-in-mycobacteria-is-regulated-by-the-novel-signal-transduction-atpase-inir-in-response-to-trehalose
#13
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/29274493/1-3-5-triazaspiro-5-5-undeca-2-4-dienes-as-selective-mycobacterium-tuberculosis-dihydrofolate-reductase-inhibitors-with-potent-whole-cell-activity
#14
Xuan Yang, Wassihun Wedajo, Yoshiyuki Yamada, Sue-Li Dahlroth, Jason Jun-Long Neo, Thomas Dick, Wai-Keung Chui
The emergence of multi- and extensively-drug resistant tubercular (MDR- and XDR-TB) strains of mycobacteria has limited the use of existing therapies, therefore new drugs are needed. Dihydrofolate reductase (DHFR) has recently attracted much attention as a target for the development of anti-TB agents. This study aimed to develop selective M. tuberculosis DHFR inhibitors using rationale scaffolding design and synthesis, phenotype-oriented screening, enzymatic inhibitory study, whole cell on-target validation, molecular modeling, and in vitro DMPK determination to derive new anti-TB agents...
December 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29274054/prevalence-and-risk-factors-of-mycobacterial-infections-in-farm-and-trade-cattle-in-southwestern-nigeria
#15
Victor O Akinseye, Muideen D Adebayo, Oghenekaro O Genesis, Olubukola D Adelakun, Simeon I B Cadmus
We evaluated the prevalence of mycobacterial infections (i.e., Mycobacterium bovis and non-tuberculous mycobacteria [NTM]) and their associated risk factors among cattle herds and trade cattle in southwestern Nigeria. Through cross-sectional study design, cattle herds from three locations were screened using the single intradermal comparative cervical tuberculin test based on two diagnostic standards; more than 4 mm (˃ 4 mm) and more than 2 mm (˃ 2 mm) cut-off points. Abattoir study involved screening trade cattle for tuberculous lesions...
December 22, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/29260746/-the-spectrum-of-primary-drug-resistance-of-mycobacterium-tuberculosis-in-patients-with-tuberculosis-in-relation-to-human-immunodeficiency-virus-status
#16
V N Zimina, O E Mikova, T A Varetskaya, D A Oborin, S Yu Degtyareva, V I Sergevnin
AIM: To estimate the detection rate and spectrum of primary drug resistance of Mycobacterium tuberculosis (MBT) in patients with tuberculosis (TB) in relation to their human immunodeficiency virus (HIV) status in a region with high HIV infection rates (the Perm Territory) and to compare of drug-resistant MBT (DR-MBT) in patients with HIV/TB co-infection, by using phenotypic and molecular genetic testing (MGT) methods. SUBJECTS AND METHODS: The results of sputum bacteriological examination were analyzed in 178 HIV-infected patients and 354 non-HIV-infected individuals with a TB diagnosis made in the period July 1, 2014 to August 1, 2015...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29259589/complete-genome-sequencing-of-mycobacterium-bovis-sp38-and-comparative-genomics-of-mycobacterium-bovis-and-m-tuberculosis-strains
#17
Cristina Kraemer Zimpel, Paulo E Brandão, Antônio F de Souza Filho, Robson F de Souza, Cássia Y Ikuta, José Soares Ferreira Neto, Naila C Soler Camargo, Marcos Bryan Heinemann, Ana M S Guimarães
Mycobacterium bovis causes bovine tuberculosis and is the main organism responsible for zoonotic tuberculosis in humans. We performed the sequencing, assembly and annotation of a Brazilian strain of M. bovis named SP38, and performed comparative genomics of M. bovis genomes deposited in GenBank. M. bovis SP38 has a traditional tuberculous mycobacterium genome of 4,347,648 bp, with 65.5% GC, and 4,216 genes. The majority of CDSs (2,805, 69.3%) have predictive function, while 1,206 (30.07%) are hypothetical. For comparative analysis, 31 M...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29250924/non-tuberculous-mycobacteria-isolated-from-lymph-nodes-and-faecal-samples-of-healthy-slaughtered-cattle-and-the-abattoir-environment
#18
G Ghielmetti, U Friedel, S Scherrer, E Sarno, P Landolt, O Dietz, M Hilbe, C Zweifel, R Stephan
Infections caused by non-tuberculous mycobacteria (NTM) are reported as emerging disease in many countries worldwide. The occurrence of NTM in different hosts and their implication as obligate or opportunistic pathogen remain largely unclear. Lymph nodes and faecal samples of clinically healthy Swiss cattle at slaughter were analysed for the presence of NTM. Based on the examined lymph nodes, NTM were detected in 20% of 108 cattle originating from different premises. The 22 isolates belonged to five different species of Mycobacteria (M...
December 17, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29249639/t-cells-primed-by-live-mycobacteria-versus-a-tuberculosis-subunit-vaccine-exhibit-distinct-functional-properties
#19
Thomas Lindenstrøm, Albanus Moguche, Mie Damborg, Else Marie Agger, Kevin Urdahl, Peter Andersen
Despite inducing strong T cell responses, Mycobacterium tuberculosis (Mtb) infection fails to elicit protective immune memory. As such latently infected or successfully treated Tuberculosis (TB) patients are not protected against recurrent disease. Here, using a mouse model of aerosol Mtb infection, we show that memory immunity to H56/CAF01 subunit vaccination conferred sustained protection in contrast to the transient natural immunity conferred by Mtb infection. Loss of protection to re-infection in natural Mtb memory was temporally linked to an accelerated differentiation of ESAT-6- and to a lesser extent, Ag85B-specific CD4 T cells in both the lung parenchyma and vasculature...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29247728/glycine-rich-loop-encompassing-active-site-at-interface-of-hexameric-m-tuberculosis-eis-protein-contributes-to-its-structural-stability-and-activity
#20
Shashi Anand, Charu Sharma
RvEis is a crucial thermostable hexameric aminoglycoside acetyltransferase of Mycobacterium tuberculosis, overexpression of which confers Kanamycin resistance in clinical strains. The thermostability associated with hexameric RvEis is important for the enhanced intracellular survival of mycobacteria. However, the structural determinants responsible for its thermal stability remain unexplored. In this study, we have assessed the role of glycines of conserved glycine-rich motif (G123GIYG127) present at the oligomeric interface in the hydrophobic core of RvEis in sustenance of its structural stability, oligomerization and functional activity...
December 13, 2017: International Journal of Biological Macromolecules
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