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Mycobacterium tuberculosis

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https://www.readbyqxmd.com/read/28103537/hybrids-of-thienopyrimidinones-and-thiouracils-as-anti-tubercular-agents-sar-and-docking-studies
#1
Mahesh M Pisal, Laxman U Nawale, Manoj D Patil, Sujit G Bhansali, Jayant M Gajbhiye, Dhiman Sarkar, Subhash P Chavan, Hanumant B Borate
A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (MIC 7.6-19.1 μg/mL, 12-35 μM) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 μg/mL, 41 μM) as well as active (MIC 25.4 μg/mL, 45 μM) stage. Structural modifications of the compound 15 were carried out to study the structure-activity relationship and it was observed that the compound 18 exhibited antitubercular activity comparable to the compound 15...
January 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28103313/mycobacterium-marinum-degrades-both-triacylglycerols-and-phospholipids-from-its-dictyostelium-host-to-synthesise-its-own-triacylglycerols-and-generate-lipid-inclusions
#2
Caroline Barisch, Thierry Soldati
During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28102559/effect-of-bone-like-hydroxyapatite-poly-amino-acid-loaded-with-rifapentine-microspheres-on-bone-and-joint-tuberculosis-in-vitro
#3
Yuwu Liu, Dianming Jiang
Rifapentine-loaded poly(lactic-co-glycolic acid) microspheres (RPMs)-loaded bone-like hydroxyapatite/poly amino acid (BHA/PAA) is effective in curing S. aureus-induced chronic osteomyelitis. This study continues to investigate the effect of RPM-loaded BHA/PAA on the bacterial growth of Mycobacterium tuberculosis (MTB), cell proliferation and differentiation in MTB H37Rv-infected MG63 cells. Furthermore, whether Wnt/β-catenin signaling pathway was activated by RPM-loaded BHA/PAA was explored. We found the bactec growth index of H37Rv was significantly inhibited by RPM-loaded BHA/PAA...
January 19, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28100768/control-of-bovine-tuberculosis-in-a-farmed-red-deer-herd-in-england
#4
F Busch, F Bannerman, S Liggett, F Griffin, J Clarke, K P Lyashchenko, S Rhodes
This report describes how Mycobacterium bovis infection was controlled and eventually eradicated in a farmed red deer herd in the north of England, following sustained tuberculin skin testing supplemented with serological (antibody) tests over a period of approximately two years. By taking advantage of the anamnestic antibody response produced by the skin test to detect skin test-negative, antibody-positive infected individuals, a total of 35 additional animals were identified, including 2 with gross visible lesions typical of bovine tuberculosis (BTB)...
January 18, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28100602/find-tuberculosis-strain-bank-a-resource-for-researchers-and-developers-working-on-tests-to-detect-mycobacterium-tuberculosis-and-related-drug-resistance
#5
Belay Tessema, Pamela Nabeta, Eloise Valli, Audrey Albertini, Jimena Collantes, Nguyen Huu Lan, Elena Romancenco, Nestani Tukavdze, Claudia M Denkinger, David L Dolinger
BACKGROUND: The spread of multidrug-resistant tuberculosis and extensively drug-resistant TB hampers the global efforts in the fight against tuberculosis. To enhance the development and evaluation of diagnostic tests quickly and efficiently, well characterized strains and samples from drug resistant tuberculosis patients are necessary. In this project, FIND has focused on the collection, characterization and storage of such well-characterized reference materials and to make them available to researchers and developers...
January 18, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28100546/accuracy-of-line-probe-assays-for-the-diagnosis-of-pulmonary-and-multidrug-resistant-tuberculosis-a-systematic-review-and-meta-analysis
#6
Ruvandhi R Nathavitharana, Patrick G T Cudahy, Samuel G Schumacher, Karen R Steingart, Madhukar Pai, Claudia M Denkinger
Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed.This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28099836/antibodies-to-mycobacterium-tuberculosis
#7
Arturo Casadevall
No abstract text is available yet for this article.
19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28099825/transmission-of-extensively-drug-resistant-tuberculosis-in-south-africa
#8
N Sarita Shah, Sara C Auld, James C M Brust, Barun Mathema, Nazir Ismail, Pravi Moodley, Koleka Mlisana, Salim Allana, Angela Campbell, Thuli Mthiyane, Natashia Morris, Primrose Mpangase, Hermina van der Meulen, Shaheed V Omar, Tyler S Brown, Apurva Narechania, Elena Shaskina, Thandi Kapwata, Barry Kreiswirth, Neel R Gandhi
Background Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. Methods We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014...
19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28098814/thioridazine-a-non-antibiotic-drug-highly-effective-in-combination-with-first-line-anti-tuberculosis-drugs-against-any-form-of-antibiotic-resistance-of-mycobacterium-tuberculosis-due-to-its-multi-mechanisms-of-action
#9
REVIEW
Leonard Amaral, Miguel Viveiros
This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb...
January 14, 2017: Antibiotics
https://www.readbyqxmd.com/read/28098168/the-il-17a-rs2275913-single-nucleotide-polymorphism-is-associated-with-protection-to-tuberculosis-but-related-to-higher-disease-severity-in-argentina
#10
A Rolandelli, R E Hernández Del Pino, J M Pellegrini, N L Tateosian, N O Amiano, S de la Barrera, N Casco, M Gutiérrez, D J Palmero, V E García
Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#11
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096545/thiazomycin-nocathiacin-and-analogs-show-strong-activity-against-clinical-strains-of-drug-resistant-mycobacterium-tuberculosis
#12
Sheo B Singh, Libo Xu, Peter T Meinke, Natalia Kurepina, Barry N Kreiswirth, David B Olsen, Katherine Young
Thiazolyl peptides are a class of natural products with potent Gram-positive antibacterial activities. Lack of aqueous solubility precluded this class of compounds from advancing to clinical evaluations. Nocathiacins and thiazomycins are sub-classes of thiazolyl peptides that are endowed with structural features amenable for chemical modifications. Semi-synthetic modifications of nocathiacin led to a series of analogs with improved water solubility, while retaining potency and antibacterial spectrum. We studied the activities of a selection of two natural products (nocathiacin and thiazomycin) as well as seven polar semi-synthetic analogs against twenty clinical strains of Mycobacterium tuberculosis with MDR phenotypes...
January 18, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28096490/comprehensive-essentiality-analysis-of-the-mycobacterium-tuberculosis-genome-via-saturating-transposon-mutagenesis
#13
Michael A DeJesus, Elias R Gerrick, Weizhen Xu, Sae Woong Park, Jarukit E Long, Cara C Boutte, Eric J Rubin, Dirk Schnappinger, Sabine Ehrt, Sarah M Fortune, Christopher M Sassetti, Thomas R Ioerger
: For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096448/loss-of-function-mutations-in-hspr-rescue-the-growth-defect-of-a-mycobacterium-tuberculosis-proteasome-activator-e-pafe-mutant
#14
Jordan B Jastrab, Marie I Samanovic, Richard Copin, Bo Shopsin, K Heran Darwin
: Mycobacterium tuberculosis uses a proteasome to degrade proteins by both ATP-dependent and -independent pathways. While much has been learned about ATP-dependent degradation, relatively little is understood about the ATP-independent pathway, which is controlled by Mycobacterium tuberculosis proteasome accessory factor E (PafE). Recently, we found that a Mycobacterium tuberculosis pafE mutant has slowed growth in vitro and is sensitive to killing by heat stress. However, we did not know if these phenotypes were caused by an inability to degrade the PafE-proteasome substrate HspR (heat shock protein repressor), an inability to degrade any damaged or misfolded proteins, or a defect in another protein quality control pathway...
January 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28096157/resistance-to-thiacetazone-derivatives-active-against-mycobacterium-abscessus-involves-mutations-in-the-mmpl5-transcriptional-repressor-mab_4384
#15
Iman Halloum, Albertus Viljoen, Varun Khanna, Derek Craig, Christiane Bouchier, Roland Brosch, Geoffrey Coxon, Laurent Kremer
Available chemotherapeutic options are very limited against Mycobacterium abscessus, which imparts a particular challenge in the treatment of cystic fibrosis (CF) patients infected with this rapid-growing mycobacterium. New drugs are urgently needed against this emerging pathogen, but the discovery of active chemotypes has not been performed intensively. Interestingly, however, the repurposing of thiacetazone (TAC), a drug once used to treat tuberculosis, has increased following the deciphering of its mechanism of action and the detection of significantly more potent analogues...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28095790/comparison-of-loop-mediated-isothermal-amplification-assay-and-smear-microscopy-with-culture-for-the-diagnostic-accuracy-of-tuberculosis
#16
Baye Gelaw, Yitayal Shiferaw, Marta Alemayehu, Abate Assefa Bashaw
BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required. Hence, we assessed the diagnostic performance of Loop-mediated isothermal amplification (LAMP) assay in detecting M.tuberculosis infection in sputum sample compared to LED fluorescent smear microscopy and culture...
January 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28095608/esx-1-and-phthiocerol-dimycocerosates-of-mycobacterium-tuberculosis-act-in-concert-to-cause-phagosomal-rupture-and-host-cell-apoptosis
#17
Jacques Augenstreich, Ainhoa Arbues, Roxane Simeone, Evert Haanappel, Alice Wegener, Fadel Sayes, Fabien Le Chevalier, Christian Chalut, Wladimir Malaga, Christophe Guilhot, Roland Brosch, Catherine Astarie-Dequeker
Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT-6). This small protein, which is secreted by the type VII secretion system ESX-1 (T7SS/ESX-1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28095429/high-rates-of-non-tuberculous-mycobacteria-isolation-in-mozambican-children-with-presumptive-tuberculosis
#18
Elisa López-Varela, Alberto L García-Basteiro, Orvalho J Augusto, Oscar Fraile, Helder Bulo, Tasmiya Ira, Kizito Gondo, Jakko van Ingen, Denise Naniche, Jahit Sacarlal, Pedro L Alonso
INTRODUCTION: Non-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique. METHODS: This study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays...
2017: PloS One
https://www.readbyqxmd.com/read/28094223/anti-tuberculosis-activity-and-structure-activity-relationships-of-oxygenated-tricyclic-carbazole-alkaloids-and-synthetic-derivatives
#19
Carsten Börger, Christian Brütting, Konstanze K Julich-Gruner, Ronny Hesse, V Pavan Kumar, Sebastian K Kutz, Marika Rönnefahrt, Claudia Thomas, Baojie Wan, Scott G Franzblau, Hans-Joachim Knölker
A series of 49 oxygenated tricyclic carbazole derivatives has been tested for inhibition of the growth of Mycobacterium tuberculosis and a mammalian cell line (vero cells). From this series, twelve carbazoles showed a significant anti-TB activity. The four most active compounds were the naturally occurring carbazole alkaloids clauszoline-M (45), murrayaline-C (41), carbalexin-C (27), and the synthetic carbazole derivative 22 with MIC90 values ranging from 1.5 to 3.7μM. The active compounds were virtually nontoxic for the mammalian cell line in the concentration range up to 50μM...
December 27, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28092930/prevalence-of-latent-tuberculosis-among-laboratory-healthcare-workers-in-iran-a-cross-sectional-study
#20
Mahshid Nasehi, Abdolrazagh Hashemi-Shahraki, Amin Doosti-Irani, Saeed Sharafi, Ehsan Mostafavi
Objectives: The risk of transmission of Mycobacterium tuberculosis from patients to health-care workers (HCWs) is a neglected problem in many countries including Iran. The aim of this study was to estimate the prevalence of latent tuberculosis infection (LTBI), and related risk factors among TB laboratory staff in Iran. Methods: All TB laboratory staff (689 individual) who were working in TB laboratories of 50 Iranian Universities of Medical Sciences and a random sample consisted of 317 participants from low risk HCWs, were included in this cross sectional study...
December 30, 2016: Epidemiology and Health
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