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https://www.readbyqxmd.com/read/28820946/proteogenomic-investigation-of-strain-variation-in-clinical-mycobacterium-tuberculosis-isolates
#1
Tiaan Heunis, Anzaan Dippenaar, Robin M Warren, Paul D van Helden, Ruben G van der Merwe, Nicolaas C Gey van Pittius, Arnab Pain, Samantha L Sampson, David L Tabb
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28820943/the-active-site-flexibility-of-mycobacterium-tuberculosis-isocitrate-lyase-in-dimer-form
#2
Yie-Vern Lee, Sybing Choi, Habibah Wahab, Yee Siew Choong
Tuberculosis (TB) still remains as global threat due to the emerging of drug resistant strain. Instead of focus on drug target of active stage TB, we are highlighting the isocitrate lyase (ICL) at the dormant stage TB. ICL is one of the persistent factors for Mycobacterium tuberculosis (MTB) to survive during dormant phase. In addition, the absent of ICL in human has made ICL a potential drug target for TB therapy. However, the dynamics details of ICL which could give insights to the ICL-ligand interaction is yet to be solved...
August 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28820170/paradoxical-worsening-of-a-case-of-tb-subretinal-abscess-with-serpiginous-like-choroiditis-following-the-initiation-of-antitubercular-therapy
#3
Sudha K Ganesh, B Sowkath Ali
A 37-year-old immunocompetent male patient presented with the blurring of vision, both eyes for the past1 year. Fundus examination revealed bilateral multiple subretinal abscesses with areas of healed serpiginous-like choroiditis. Laboratory investigations showed positive tuberculin skin test, positive QuantiFERON TB-Gold Test, and high resolution computed tomography chest showed enlarged mediastinal lymph nodes. The aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome)...
August 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28819600/extensively-drug-resistant-tuberculosis-of-the-lumbar-spine-in-a-six-year-old-child-a-case-report
#4
Siddharth Sanjay Shah, Aakanksha Arvind Goregaonkar, Arvind Balkrishna Goregaonkar
INTRODUCTION: The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a challenging paradigm shift faced by the TB control programs worldwide today. The treatment is further compounded with unique management difficulties faced in pediatric patients. Treatment of XDR-TB requires prolonged chemotherapy with second-line drugs which offer lesser potency and increased risk of drug-related side effects. We present a case of spinal XDR-TB in a child, managed with extended second-line antitubercular chemotherapy (ATT)...
March 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/28819499/multiple-jejunal-perforation-secondary-to-intestinal-tuberculosis-infection-a-case-report
#5
Anthony Lyonga Ngonge, Domin Sone Majunda Ekaney, Carlson-Babila Sama, Joffi Musonge-Effoe, Valery Sammah Effoe, Gerald Ekwen
Abdominal tuberculosis (TB) may affect any part of the gastrointestinal tract resulting in significant morbidity and mortality. There is an increase in the incidence of abdominal TB favored by the emergence of multi-drug resistant Mycobacterium tuberculosis and immunosuppression especially from HIV co-infection. Our case is that of a 31 year old HIV-positive woman, adherent to antiretroviral therapy, who presented with a 2 month history of progressive abdominal distention, drenching night sweat and fatigue, but without fever...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28819247/delta-inulin-based-adjuvants-promote-the-generation-of-polyfunctional-cd4-t-cell-responses-and-protection-against-mycobacterium-tuberculosis-infection
#6
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, Nikolai Petrovsky, James A Triccas
There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819202/mechanism-of-transformation-in-mycobacteria-using-a-novel-shockwave-assisted-technique-driven-by-in-situ-generated-oxyhydrogen
#7
Akshay Datey, Janardhanraj Subburaj, Jagadeesh Gopalan, Dipshikha Chakravortty
We present a novel method for shockwave-assisted bacterial transformation using a miniature oxyhydrogen detonation-driven shock tube. We have obtained transformation efficiencies of about 1.28 × 10(6), 1.7 × 10(6), 5 × 10(6), 1 × 10(5), 1 × 10(5) and 2 × 10(5) transformants/µg of DNA for Escherichia coli, Salmonella Typhimurum, Pseudomonas aeruginosa, Mycobacterium smegmatis, Mycobacterium tuberculosis (Mtb) and Helicobacter pylori respectively using this method which are significantly higher than those obtained using conventional methods...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818767/recent-advances-of-pyrazole-containing-derivatives-as-anti-tubercular-agents
#8
Zhi Xu, Chuan Gao, Qing-Cheng Ren, Xu-Feng Song, Lian-Shun Feng, Zao-Sheng Lv
One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium tuberculosis (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles...
August 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28818565/raw-starch-microparticles-have-immunostimulant-activity-in-mice-vaccinated-with-bcg-and-challenged-with-mycobacterium-tuberculosis
#9
Silvia Moreno-Mendieta, Jorge Barrios-Payán, Dulce Mata-Espinosa, Sergio Sánchez, Rogelio Hernández-Pando, Romina Rodríguez-Sanoja
The main challenge for vaccine development or improvement is the lack of safe adjuvants or immunostimulants that induce protective immune responses and can be used for mucosal immunization, which is a highly desirable strategy for vaccination against infectious diseases acquired by oral or intranasal routes. One promising alternative is the use of biodegradable and biocompatible polymeric microparticles. Recently, we developed an immobilization and delivery system with starch microparticles (SMPs) and a starch-binding domain (SBDtag) suitable for the mucosal administration of antigens and the induction of antigen-specific immune responses...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28818102/field-evaluation-of-the-efficacy-of-mycobacterium-bovis-bcg-vaccine-against-tuberculosis-in-goats
#10
Enric Vidal, Claudia Arrieta-Villegas, Miriam Grasa, Irene Mercader, Mariano Domingo, Bernat Pérez de Val
BACKGROUND: Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. RESULTS: Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy...
August 17, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28817682/experimental-study-of-tuberculosis-from-animal-models-to-complex-cell-systems-and-organoids
#11
REVIEW
Kaori L Fonseca, Pedro N S Rodrigues, I Anna S Olsson, Margarida Saraiva
Tuberculosis (TB) is a devastating disease to mankind that has killed more people than any other infectious disease. Despite many efforts and successes from the scientific and health communities, the prospect of TB elimination remains distant. On the one hand, sustainable public health programs with affordable and broad implementation of anti-TB measures are needed. On the other hand, achieving TB elimination requires critical advances in three areas: vaccination, diagnosis, and treatment. It is also well accepted that succeeding in advancing these areas requires a deeper knowledge of host-pathogen interactions during infection, and for that, better experimental models are needed...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28817643/peripheral-clinic-versus-centralized-laboratory-based-xpert-mtb-rif-performance-experience-gained-from-a-pragmatic-stepped-wedge-trial-in-botswana
#12
Tefera Agizew, Rosanna Boyd, Ndwapi Ndwapi, Andrew Auld, Joyce Basotli, Sambayawo Nyirenda, Zegabriel Tedla, Anikie Mathoma, Unami Mathebula, Chawangwa Lesedi, Sherri Pals, Anand Date, Heather Alexander, Thomas Kuebrich, Alyssa Finlay
BACKGROUND: In 2011, the Botswana National Tuberculosis Program adopted World Health Organization guidelines and introduced Xpert MTB/RIF (Xpert) assay to support intensified case finding among people living with HIV enrolling in care. An evaluation was designed to assess performance under operational conditions to inform the national Xpert scale-up. METHODS: Xpert was implemented from August 2012 through November 2014 with 13 GeneXpert instruments (GeneXpert) deployed in a phased approach over nine months: nine centralized laboratory and four point-of-care (POC) peripheral clinics...
2017: PloS One
https://www.readbyqxmd.com/read/28816372/in-vitro-antitubercular-activity-of-3-deoxysappanchalcone-isolated-from-the-heartwood-of-caesalpinia-sappan-linn
#13
Hoonhee Seo, Sukyung Kim, Hafij Al Mahmud, Md Imtiazul Islam, Kung-Woo Nam, Byung-Eui Lee, Hanna Lee, Myoung-Lae Cho, Heung-Mook Shin, Ho-Yeon Song
Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic. New drugs are urgently needed to combat the growing threat of antimicrobial resistance. To achieve this goal, we screened approximately 500 species of medicinal plant methanol extracts and their solvent partitioned fractions for potential inhibitors of Mycobacterium tuberculosis growth...
August 17, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28815923/biophysical-screening-of-a-focused-library-for-the-discovery-of-cyp121-inhibitors-as-novel-antimycobacterials
#14
Christian Brengel, Andreas Thomann, Alexander Schifrin, Giuseppe Allegretta, Ahmed A M Kamal, Joerg Haupenthal, Isabell Schnorr, Sang Hyun Cho, Scott Gary Franzblau, Martin Empting, Jens Eberhard, Rolf W Hartmann
The development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multi-drug resistance (MDR) combined with a complicated long-term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods. Best hits originating from only one structural class gave first information about molecular motifs required for binding and activity...
August 16, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28815830/determinants-of-the-inhibition-of-dpre1-and-cyp2c9-by-antitubercular-thiophenes
#15
Renhe Liu, Xiaoxuan Lyu, Mei-Hui Hsu, Catherine Vilcheze, Scott G Franzblau, William R Jacobs, Gurdyal S Besra, Eric F Johnson, Klaus Fütterer, Feng Wang
Mycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X-ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9...
August 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28813625/detection-of-first-line-drug-resistance-mutations-and-drug-protein-interaction-dynamics-from-tuberculosis-patients-in-south-india
#16
Somanna Ajjamada Nachappa, Sumana M Neelambike, Chokkanna Amruthavalli, Nallur B Ramachandra
Diagnosis of drug-resistant tuberculosis predominantly relies on culture-based drug susceptibility testing, which take weeks to produce a result and a more time-efficient alternative method is multiplex allele-specific PCR (MAS-PCR). Also, understanding the role of mutations in causing resistance helps better drug designing. AIMS: To evaluate the ability of MAS-PCR in the detection of drug resistance and to understand the mechanism of interaction of drugs with mutant proteins in Mycobacterium tuberculosis...
August 16, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28813434/detection-of-anti-hspx-antibodies-and-hspx-protein-in-patient-sera-for-the-identification-of-recent-latent-infection-by-mycobacterium-tuberculosis
#17
Jorge Castro-Garza, Paola García-Jacobo, Lydia G Rivera-Morales, Frederick D Quinn, James Barber, Russell Karls, Debra Haas, Shelly Helms, Tuhina Gupta, Henry Blumberg, Jane Tapia, Itza Luna-Cruz, Adrián Rendon, Javier Vargas-Villarreal, Lucio Vera-Cabrera, Cristina Rodríguez-Padilla
Mycobacterium tuberculosis is a pathogen causing tuberculosis (TB) a spectrum of disease including acute and asymptomatic latent stages. Identifying and treating latently-infected patients constitutes one of the most important impediments to TB control efforts. Those individuals can remain undiagnosed for decades serving as potential reservoirs for disease reactivation. Tests for the accurate diagnosis of latent infection currently are unavailable. HspX protein (α-crystallin), encoded by Rv2031c gene, is produced in vitro by M...
2017: PloS One
https://www.readbyqxmd.com/read/28812370/rauvolfianine-a-new-antimycobacterial-glyceroglycolipid-and-other-constituents-from-rauvolfia-caffra-sond-apocynaceae
#18
Robert Ebeh Messanga, Ngono Bikobo Dominique Serge, Auguste Abouem A Zintchem, Mbabi Nyemeck Ii Norbert, Moni Ndedi Esther Del Florence, Betote Diboué Patrick Hervé, Nyegue Maximilienne Ascension, Atchadé Alex De Théodore, Pegnyemb Dieudonné Emmanuel, Bochet Christian G, Ulrich Koert
The chemical investigation of the extract of the dried leaves of Rauvolfia caffra (Sond) (synonym Rauvolfia macrophylla) (Apocynaceae) led to isolation of a new glycoside derivative, rauvolfianine (1) as well as six known compounds: oleanolic acid (2), sitosterol-3-O-β-D-glucopyranoside (3), betulinic acid (4), vellosimine (5), sarpagine (6) and D-fructofuranosyl-β-(2→1)-α-D-glucopyranoside (7). Compounds 1, 2, 3, 4 and 7 were evaluated for antitubercular activity. Compounds 1 and 2 were the most active (MIC = 7...
August 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28812125/recombinant-expression-and-biochemical-characterization-of-mycobacterium-tuberculosis-3fe-4s-ferredoxin-rv1786
#19
Yun Lu, Feng Qiao, Yue Li, Xiao-Hong Sang, Cong-Ran Li, Jian-Dong Jiang, Xin-Yi Yang, Xue-Fu You
Ferredoxins are iron-sulfur protein that mediate electron transfer in cytochrome P450 mono-oxygenase (CYP)-related catalytic reactions in a wide variety of organisms. Rv1786 is a putative ferredoxin, encoded by a gene located downstream of the gene encoding CYP143A1 in the Mycobacterium tuberculosis genome. However, the structure and function of Rv1786 have remained unclear. Here, the recombinant Mtb Rv1786 was expressed, purified as a His-tagged form and characterized with [3Fe-4S] clusters as its cofactors using a series of measurements including SDS-PAGE, western blot, UV/Visible, MALDI-TOF/TOF-MS, and electron paramagnetic resonance spectroscopic analysis...
August 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28811595/delayed-effects-of-transcriptional-responses-in-mycobacterium-tuberculosis-exposed-to-nitric-oxide-suggest-other-mechanisms-involved-in-survival
#20
Teresa Cortes, Olga T Schubert, Amir Banaei-Esfahani, Ben C Collins, Ruedi Aebersold, Douglas B Young
Mycobacterium tuberculosis has succeeded as a human pathogen for tens of thousands of years thanks to its ability to resist and adapt to the adverse conditions it encounters upon infection. Bacterial adaptation to stress is commonly viewed in the context of transcriptional regulation, with the implicit expectation that an initial transcriptomic response is tightly coupled to an ensuing proteomic response. However, after challenging M. tuberculosis with nitric oxide we found that the rapid transcriptional responses, detectable within minutes of nitric oxide exposure, typically took several hours to manifest on the protein level...
August 15, 2017: Scientific Reports
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