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https://www.readbyqxmd.com/read/28938588/calreticulin-modulates-the-intracellular-survival-of-mycobacteria-by-regulating-er-stress-mediated-apoptosis
#1
Sung Hee Jo, Ji-Ae Choi, Yun-Ji Lim, Junghwan Lee, Soo-Na Cho, Sung-Man Oh, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937879/advax4-delta-inulin-combination-adjuvant-together-with-ecmx-a-fusion-construct-of-three-protective-mtb-antigens-induces-a-potent-th1-immune-response-and-protects-mice-against-mycobacterium-tuberculosis-infection
#2
Bruno de Paula Oliveira Santos, Monalisa Martins Trentini, Renato Beilner Machado, Mara Rúbia Nunes Celes, André Kipnis, Nikolai Petrovsky, Ana Paula Junqueira-Kipnis
Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMXformulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. When BALB/c mice were immunized three times intramuscularly with these vaccine formulationsInjection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b(+)) in the draining lymph nodes consistent with a chemotactic adjuvant effect...
September 22, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28937657/synthesis-of-2-4-diaminopyrimidine-core-based-derivatives-and-biological-evaluation-of-their-anti-tubercular-activities
#3
Yifan Ouyang, Hao Yang, Peng Zhang, Yu Wang, Sargit Kaur, Xuanli Zhu, Zhe Wang, Yutong Sun, Wei Hong, Yun Fong Ngeow, Hao Wang
Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28935874/concordant-and-discordant-gene-expression-patterns-in-mouse-strains-identify-best-fit-animal-model-for-human-tuberculosis
#4
Teresa Domaszewska, Lisa Scheuermann, Karin Hahnke, Hans Mollenkopf, Anca Dorhoi, Stefan H E Kaufmann, January Weiner
Immunity in infection, inflammation and malignancy differs markedly in man and mouse. Still, we learn about human immunity in large extent from experimental mouse models. We propose a novel data integration approach which identifies concordant and discordant gene expression patterns of the immune responses in heterologous data sets. We have conducted experiments to compare human and murine transcriptional responses to Mycobacterium tuberculosis (Mtb) infection in whole blood (WB) as well as macrophages and compared them with simulated as well as publicly available data...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935371/a-sir2-family-protein-rv1151c-deacetylates-hu-to-alter-its-dna-binding-mode-in-mycobacterium-tuberculosis
#5
Chinmay Anand, Rajni Garg, Soumitra Ghosh, Valakunja Nagaraja
Till recently, knowledge about epigenetic regulation in bacterial world confined largely to DNA methylation. Lysine acetylation/deacetylation of histones is a major contributor for chromatin dynamics in eukaryotes. However, little is known about such epigenetic changes brought about by post-translational modifications in bacteria. Here, we describe an example of such mechanism occurring in a histone like protein, HU from Mycobacterium tuberculosis (Mtb). Previously, we demonstrated the interaction and acetylation of Mtb HU (MtHU) by one of the acetyl transferases, Eis...
September 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28934422/low-frequency-of-acquired-isoniazid-and-rifampicin-resistance-in-rifampicin-susceptible-pulmonary-tuberculosis-in-a-setting-of-high-hiv-1-infection-and-tuberculosis-coprevalence
#6
Neesha Rockwood, Frederick Sirgel, Elizabeth Streicher, Robin Warren, Graeme Meintjes, Robert J Wilkinson
Background: We estimated the incidence of acquired isoniazid and rifampicin resistance in rifampicin-susceptible tuberculosis in a setting of high human immunodeficiency virus type 1 (HIV-1) infection and tuberculosis coprevalence. Methods: GeneXpert MTB/RIF-confirmed patients with rifampicin-susceptible tuberculosis were recruited at antituberculosis treatment initiation in Khayelitsha, South Africa. Liquid culture and adherence assessment were performed at 2 and 5-6 months...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28933243/drug-targets-in-dormant-mycobacterium-tuberculosis-can-the-conquest-against-tuberculosis-become-a-reality
#7
Vivek Kumar Gupta, M Madhan Kumar, Dharmendra Singh, Deepa Bisht, Shweta Sharma
Targeting M. tuberculosis (Mtb) in latent form of infection is a major obstacle and big challenge in tuberculosis (TB) eradication by current chemotherapy. A better understanding of the physiology of Mtb and of the metabolic state of the bacillus during the dormancy, is a primary need in finding drug targets against non replicating persistent (NRP) form of the Mtb. Identification of potential drug targets against dormant state of Mtb is critically important to achieve the goal of complete eradication for shortening of anti-TB therapy...
September 21, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28931830/circulating-mycobacterium-tuberculosis-dosr-latency-antigen-specific-polyfunctional-regulatory-il10-th17-cd4-t-cells-differentiate-latent-from-active-tuberculosis
#8
Srabanti Rakshit, Vasista Adiga, Soumya Nayak, Pravat Nalini Sahoo, Prabhat Kumar Sharma, Krista E van Meijgaarden, Anto Jesuraj Uk J, Chirag Dhar, George D Souza, Greg Finak, Stephen C De Rosa, Tom H M Ottenhoff, Annapurna Vyakarnam
The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931561/genetic-mimetics-of-mycobacterium-tuberculosis-and-methicillin-resistant-staphylococcus-aureus-as-verification-standards-for-molecular-diagnostics
#9
Edith Erika Machowski, Bavesh Davandra Kana
Molecular diagnostics have revolutionized the management of health care through enhanced detection of disease or infection and effective engagement into care. In recognition of this, the World Health Organization approved the rollout out of nucleic acid amplification technologies for identification of Mycobacterium tuberculosis using platforms such as GeneXpert MTB/RIF, the GenoType MTBDRplus Line Probe Assay and more recently, GeneXpert MTB/RIF Ultra. These assays can simultaneously detect tuberculosis infection and assess rifampicin resistance...
September 20, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28924924/predictors-of-microbiologically-confirmed-intrathoracic-tuberculosis
#10
Rakhi Jain, Aparna Mukherjee, Mohit Singla, Yogita Verma, Hitender Gautam, Rakesh Lodha, Urvashi B Singh, Sushil K Kabra
OBJECTIVE: To identify risk factors for microbiologically confirmed intrathoracic tuberculosis in children. METHODS: Children, 6 mo to 15 y of age, attending the out-patient department of a tertiary care centre in India, with probable intrathoracic tuberculosis were enrolled. Microbiological confirmation of tuberculosis was defined as positivity on smear (Ziehl-Neelsen staining) and/or Xpert MTB/RIF and/or MGIT-960 culture. Association of various factors with microbiological confirmation were assessed by univariate and multivariate analysis...
September 19, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28924198/bacteriological-diagnosis-of-childhood-tb-a-prospective-observational-study
#11
Andrew J Brent, Daisy Mugo, Robert Musyimi, Agnes Mutiso, Susan Morpeth, Michael Levin, J Anthony G Scott
Childhood TB diagnosis is challenging. Studies in adults suggest Microscopic Observation Drug Susceptibility (MODS) culture or the Xpert MTB/RIF assay might be used to expand bacteriological diagnosis. However data from children are more limited. We prospectively compared MODS and Xpert MTB/RIF with standard microscopy and culture using the BD MGIT 960 system among 1442 Kenyan children with suspected TB. 97 specimens from 54 children were TB culture-positive: 91 (94%) by MGIT and 74 (76%) by MODS (p = 0...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28920697/n%C3%AE%C2%B5-and-o-acetylation-in-mycobacterium-tuberculosis-lineage-7-and-lineage-4-strains-proteins-involved-in-bioenergetics-virulence-and-antimicrobial-resistance-are-acetylated
#12
Alemayehu Godana Birhanu, Solomon Abebe Yimer, Carol Holm-Hansen, Gunnstein Norheim, Abraham Aseffa, Markos Abebe, Tone Tønjum
Increasing evidence demonstrates that lysine acetylation is involved in Mycobacterium tuberculosis (Mtb) virulence and pathogenesis. However, previous investigations in Mtb have only monitored acetylation at lysine residues using selected reference strains. We analyzed the global Nε- and O-acetylation of 3 Mtb isolates; 2 lineage 7 clinical isolates and the lineage 4 H37Rv reference strain. Quantitative acetylome analysis resulted in identification of 2490 class-I acetylation sites, among them 2349 O-acetylation and 141 Nε-acetylation sites, derived from 953 unique proteins...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28919618/molecular-detection-and-differentiation-of-mycobacterium-tuberculosis-complex-and-non-tuberculous-mycobacterium-in-the-clinical-specimens-by-real-time-pcr
#13
M M Rahman, M R Rahim, A Khaled, T A Nasir, F Nasrin, M A Hasan
Mycobacteria are subdivided into three groups: the Mycobacterium tuberculosis complex, the non-tuberculous mycobacteria called NTM or MOTT (Mycobacteria Other Than Tuberculosis) and Mycobacterium leprae. Over the past few decades, the incidence of infections caused by NTM has increased world wide. The differentiation of Mycobacterium tuberculosis complex from NTM is of primary importance for infection control and choice of antimicrobial therapy. However, there is so far no report in Bangladesh about the detection of NTM and hence differentiation of MTB and NTM...
July 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28919549/the-predominance-of-ethiopian-specific-mycobacterium-tuberculosis-families-and-minimal-contribution-of-mycobacterium-bovis-in-tuberculous-lymphadenitis-patients-in-southwest-ethiopia
#14
Mulualem Tadesse, Gemeda Abebe, Alemayehu Bekele, Mesele Bezabih, Pim de Rijk, Conor J Meehan, Bouke C de Jong, Leen Rigouts
BACKGROUND: Ethiopia has an extremely high rate of extrapulmonary tuberculosis, dominated by tuberculous lymphadenitis (TBLN). However, little is known about Mycobacterium tuberculosis complex (MTBc) lineages responsible for TBLN in Southwest Ethiopia. METHODS: A total of 304 MTBc isolates from TBLN patients in Southwest Ethiopia were genotyped primarily by spoligotyping. Isolates of selected spoligotypes were further analyzed by 15-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) (n=167) and qPCR-based single nucleotide polymorphism (n=38)...
September 15, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28919338/diagnostic-accuracy-of-xpert-mtb-rif-ultra-for-tuberculous-meningitis-in-hiv-infected-adults-a-prospective-cohort-study
#15
Nathan C Bahr, Edwin Nuwagira, Emily E Evans, Fiona V Cresswell, Philip V Bystrom, Adolf Byamukama, Sarah C Bridge, Ananta S Bangdiwala, David B Meya, Claudia M Denkinger, Conrad Muzoora, David R Boulware
BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda...
September 14, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28919337/xpert-mtb-rif-ultra-a-gamechanger-for-tuberculous-meningitis
#16
Margaret Khonga, Mark Patrick Nicol
No abstract text is available yet for this article.
September 14, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28917925/synthesis-of-synthetic-mannan-backbone-polysaccharides-found-on-the-surface-of-mycobacterium-tuberculosis-as-a-vaccine-adjuvant-and-their-immunological-properties
#17
Chakree Wattanasiri, Jiraporn Paha, Marisa Ponpuak, Somsak Ruchirawat, Siwarutt Boonyarattanakalin
Surface components of Mycobacterium tuberculosis (Mtb) play crucial roles in modulating host immune responses. Thorough understandings of immunological properties of the Mtb's surface components are essential for the development of tuberculosis treatment and prevention. Unfortunately, the accessibility to the molecules on the surface of Mtb is limited by the structural complexity due to their various macromolecular nature and the hazard of culturing Mtb. In this study, we reveal a practical synthesis of lipomannan (LM) backbone polysaccharides - the core glycans found on Mtb's surface...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#18
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912985/isolated-splenic-cold-abscesses-with-perisplenic-extension-treated-successfully-without-splenectomy
#19
Mohan Khadka, Ravi Pradhan
Splenic tuberculosis (TB) in the form of multiple splenic cold abscesses with perisplenic extensions is a rare disease, especially in an immunocompetent host. It demonstrates diagnostic complexity, which makes identification of the disease difficult. We report a case of an immunocompetent adult male who presented with fever, pain in the left lower chest, decreased appetite, and significant weight loss. On physical examination, he had tenderness in the left lower infra-axillary region and Traube's space dullness without palpable spleen...
2017: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/28912881/immune-regulation-of-mir-30-on-the-mycobacterium-tuberculosis-induced-tlr-myd88-signaling-pathway-in-thp-1-cells
#20
Yuqing Wu, Qi Sun, Liang Dai
The present study aimed to examine the expression of microRNA (miR)-30 family members in THP-1 human monocytes cells during Mycobacterium tuberculosis (MTB) H37Rv infection, and to investigate the role of miR-30 in the regulation of MTB-induced Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) activation and cytokine expression. The THP-1 cells were infected with MTB H37Rv and the expression of miR-30 family members was determined by reverse transcription-quantitative polymerase chain reaction analysis...
October 2017: Experimental and Therapeutic Medicine
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