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Tuberculosis

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https://www.readbyqxmd.com/read/28610794/molecular-mechanisms-of-action-resistance-detection-to-the-first-line-anti-tuberculosis-drugs-rifampicin-and-pyrazinamide-in-the-post-whole-genome-sequencing-era
#1
REVIEW
Ameeruddin Nusrath Unissa, Luke Elizabeth Hanna
Recent studies in addition to studies based on whole genome sequencing (WGS) of clinical isolates of Mycobacterium tuberculosis (MTB) from diverse geographical regions have provided useful insights into the mechanisms of drug resistance. Of importance, are some of the findings pertaining to mechanisms of resistance to two of the first-line anti-tuberculosis (TB) drugs, namely, rifampicin (RIF) and pyrazinamide (PZA). For example, the implication of mutations in rpoA and rpoC genes that act as compensatory mutations for those in the rpoB gene with respect to RIF resistance is noteworthy...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610793/a-novel-automatic-molecular-test-for-detection-of-multidrug-resistance-tuberculosis-in-sputum-specimen-a-case-control-study
#2
Qiang Li, Xi C Ou, Yu Pang, Hui Xia, Hai R Huang, Bing Zhao, Sheng F Wang, Yan L Zhao
MiniLab tuberculosis (ML TB) assay is a new automatic diagnostic tool for diagnosis of multidrug resistance tuberculosis (MDR-TB). This study was conducted with aims to know the performance of this assay. Sputum sample from 224 TB suspects was collected from tuberculosis suspects seeking medical care at Beijing Chest hospital. The sputum samples were directly used for smear and ML TB test. The left sputum sample was used to conduct Xpert MTB/RIF, Bactec MGIT culture and drug susceptibility test (DST). All discrepancies between the results from DST, molecular and phenotypic methods were confirmed by DNA Sequencing...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#3
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610791/the-role-of-the-time-kill-kinetics-assay-as-part-of-a-preclinical-modeling-framework-for-assessing-the-activity-of-anti-tuberculosis-drugs
#4
Hannelore I Bax, Irma A J M Bakker-Woudenberg, Corné P de Vogel, Aart van der Meijden, Annelies Verbon, Jurriaan E M de Steenwinkel
Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610790/mir-30c-is-specifically-repressed-in-patients-with-active-pulmonary-tuberculosis
#5
Silvana V Spinelli, Rocío Del V Fernández, Luciana Zoff, Bettina Bongiovanni, Ariana Díaz, Luciano D'Attilio, Natalia Santucci, Tomás Alvarez, Marcela M Marchesini, Cristina Bogue, Maria L Bay, Oscar A Bottasso
Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators. In this work, we explored whether expression of the active isoform of the glucocorticoid receptor (hGRα) in the context of the inflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610789/comparative-study-of-genotypes-of-mycobacterium-tuberculosis-from-a-northern-indian-setting-with-strains-reported-from-other-parts-of-india-and-neighboring-countries
#6
Pragya Sharma, Kiran Katoch, Shilpi Chandra, Devendra Singh Chauhan, Vishnu Dutt Sharma, David Couvin, Nalin Rastogi, Vishwa Mohan Katoch
This study was carried out to characterize Mycobacterium tuberculosis population in Ghatampur, Kanpur, North India, by spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTRs) typing. A total of 335 isolates were genotyped by spoligotyping and Central Asian (CAS) sub-lineage was the most prevalent, comprising 59.1% of all isolates. Other lineages were: East-African Indian (EAI) (19.10%), T (5.07%), Beijing (3.28%), Manu (2.98%), X (2.68%), S (0.89%), H3 (0...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610788/evaluation-of-antigen-specific-interleukin-1%C3%AE-as-a-biomarker-to-detect-cattle-infected-with-mycobacterium-bovis
#7
Mahmoud M Elnaggar, Gaber S Abdellrazeq, Alaa Elsisy, Asmaa H Mahmoud, Abdelrazeq Shyboub, Martina Sester, Samy A Khaliel, Mahavir Singh, Helmy A Torky, William C Davis
Bovine tuberculosis (bTB) is a major world-wide health problem that has been difficult to control, due to the lack of an effective vaccine and limited ability of the tuberculin skin test (TST) and the ancillary whole blood interferon-gamma (IFN-γ) release assay (IGRA) to detect all infected animals. A 6 h cytokine flow cytometric IFN-γ (CFC) assay was developed in effort to overcome these limitations and expand methods for studying the mechanisms of bTB immunopathogenesis. The present study was conducted to evaluate IL-1β as a biomarker to use in conjunction with the IFN-γ CFC assay to improve the diagnostic accuracy for bTB...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610787/spolsimilaritysearch-a-web-tool-to-compare-and-search-similarities-between-spoligotypes-of-mycobacterium-tuberculosis-complex
#8
David Couvin, Thierry Zozio, Nalin Rastogi
Spoligotyping is one of the most commonly used polymerase chain reaction (PCR)-based methods for identification and study of genetic diversity of Mycobacterium tuberculosis complex (MTBC). Despite its known limitations if used alone, the methodology is particularly useful when used in combination with other methods such as mycobacterial interspersed repetitive units - variable number of tandem DNA repeats (MIRU-VNTRs). At a worldwide scale, spoligotyping has allowed identification of information on 103,856 MTBC isolates (corresponding to 98049 clustered strains plus 5807 unique isolates from 169 countries of patient origin) contained within the SITVIT2 proprietary database of the Institut Pasteur de la Guadeloupe...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610786/a-brief-history-of-tuberculosis-in-the-czech-lands
#9
REVIEW
Lenka Vargová, Kateřina Vymazalová, Ladislava Horáčková
Tuberculosis currently remains a serious medical problem, therefore increased attention is being paid to this disease. Paleopathological studies focused on the monitoring of morbid changes in skeletal remains of historical populations facilitate a detailed study of the development of this disease. They provide direct evidence of the existence of tuberculosis and its past forms. In addition to literary and iconographic sources, the present study is focused on recording the findings of bone tuberculosis in historical osteological sets from the Czech Lands and is the starting point for their detailed review...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610785/chemokines-additional-to-ifn-%C3%AE-can-be-used-to-differentiate-among-mycobacterium-tuberculosis-infection-possibilities-and-provide-evidence-of-an-early-clearance-phenotype
#10
Ditthawat Nonghanphithak, Wipa Reechaipichitkul, Wises Namwat, Vivek Naranbhai, Kiatichai Faksri
Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON(®)-TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610784/molecular-investigation-of-active-binding-site-of-isoniazid-inh-and-insight-into-resistance-mechanism-of-s315t-mtkatg-in-mycobacterium-tuberculosis
#11
Gaurava Srivastava, Shubhandra Tripathi, Akhil Kumar, Ashok Sharma
Multi drug resistant tuberculosis is a major threat for mankind. Resistance against Isoniazid (INH), targeting MtKatG protein, is one of the most commonly occurring resistances in MDR TB strains. S315T-MtKatG mutation is widely reported for INH resistance. Despite having knowledge about the mechanism of INH, exact binding site of INH to MtKatG is still uncertain and proposed to have three presumable binding sites (site-1, site-2, and site-3). In the current study docking, molecular dynamics simulation, binding free energy estimation, principal component analysis and free energy landscape analysis were performed to get molecular level details of INH binding site on MtKatG, and to probe the effect of S315T mutation on INH binding...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610783/green-fluorescent-protein-as-a-protein-localization-and-topological-reporter-in-mycobacteria
#12
Juan Manuel Belardinelli, Mary Jackson
The cell envelope-associated proteins of Mycobacterium species play critical functions in the physiology and pathogenicity of these microorganisms. Because the determination of their subcellular localization and transmembrane topology is often critical to the understanding of their function, we investigated whether the Green Fluorescent Protein (GFP) could be used as a reporter to probe protein localization and map the topology of inner membrane proteins directly in intact mycobacterial cells. To this end, two GFP-based mycobacterial reporter plasmids were engineered and their functionality validated using a variety of membrane-associated, exported and cytosolic proteins...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610782/assessment-of-treatment-response-by-colony-forming-units-time-to-culture-positivity-and-the-molecular-bacterial-load-assay-compared-in-a-mouse-tuberculosis-model
#13
Gerjo J de Knegt, Laura Dickinson, Henry Pertinez, Dimitrios Evangelopoulos, Timothy D McHugh, Irma A J M Bakker-Woudenberg, Gerry R Davies, Jurriaan E M de Steenwinkel
The aim of the study is to compare counting of colony forming units (CFU), the time to positivity (TTP) assay and the molecular bacterial load (MBL) assay, and explore whether the last assays can detect a subpopulation which is unable to grown on solid media. CFU counting, TTP and the MBL assay were used to determine the mycobacterial load in matched lung samples of a murine tuberculosis model. Mice were treated for 24 weeks with 4 treatment arms: isoniazid (H) - rifampicin (R) - pyrazinamide (Z), HRZ-Streptomycin (S), HRZ - ethambutol (E) or ZES...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610781/pilot-studies-of-a-human-bcg-challenge-model
#14
Azra Blazevic, Mei Xia, Aldin Turan, Janice Tennant, Daniel F Hoft
Despite the great effort to develop an effective vaccine against tuberculosis (TB) there is currently no reliable and safe human challenge model that can be used for in vivo evaluation of new TB vaccine candidates and/or elucidation of the mechanisms of TB protective immunity. In this study, five volunteers were challenged with BCG intradermally (ID). Swab specimens were collected at multiple time points from the vaccination site pre- and post-vaccination to quantitate mycobacterial shedding as a surrogate of in vivo mycobacterial immunity...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610780/analysis-of-transcription-factors-micrornas-and-cytokines-involved-in-t-lymphocyte-differentiation-in-patients-with-tuberculosis-after-directly-observed-treatment-short-course
#15
Nancy Elizabeth Corral-Fernández, Juan Diego Cortes-García, Rivas-Santiago Bruno, Silvia Romano-Moreno, Susanna E Medellín-Garibay, Martín Magaña-Aquino, Raúl A Salazar-González, Roberto González-Amaro, Diana Patricia Portales-Pérez
Tuberculosis (Tb) is an infectious disease in which the immune system plays an important role. MicroRNAs are involved in the development and maintenance of CD4 + T lymphocyte subpopulations. miR-326 regulates the differentiation to Th17 cells and miR-29 correlates with the Th1 response. The aim of this study was to determine the role of microRNAs, Transcription Factors, and cytokines in Th differentiation before and after the directly observed treatment short-course (DOTS). Peripheral blood mononuclear cells and serum from Tb patients were collected at times 0 (before therapy), 2 (after the intensive phase), and 6 months (after the holding phase)...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28454656/selection-and-identification-of-specific-glycoproteins-and-glycan-biomarkers-of-macrophages-involved-in-mycobacterium-tuberculosis-infection
#16
Xiao-Lei Tang, Chun-Hui Yuan, Quanquan Ding, Yidan Zhou, Qin Pan, Xiao-Lian Zhang
Macrophages are the primary host target cells of Mycobacterium tuberculosis (M.tb). However, little is known about the changes of membrane glycopatterns of macrophages in response to M. tb infection. Using lectin microarrays we compared the differential expression of glycopatterns of macrophages upon stimulation with the heat-inactivated virulent M.tb H37Rv or attenuate M.tb H37Ra. We found that widespread alteration of macrophage membrane glycopatterns were induced by the heat-inactivated virulent M. tb H37Rv, as shown by the significantly changed binding abilities of 11 lectins (sugar binding proteins) among 40 lectins tested...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28454655/toll-like-receptor-tlr-diversity-influences-mycobacterial-growth-in-african-buffalo
#17
Nikki le Roex, Anna Jolles, Brianna Beechler, Paul van Helden, Eileen Hoal
Understanding the role of wildlife in the maintenance or spread of emerging infectious diseases is a growing priority across the world. Bovine tuberculosis (BTB) is a chronic, infectious disease caused by Mycobacterium bovis (M. bovis). BTB is widespread within game reserves in southern Africa, and within these ecosystems the primary wildlife host of this disease is the African buffalo. We used a modified bacterial killing assay for mycobacteria to investigate the effect of Toll-like receptor (TLR) genetic diversity and demographic parameters on the ability of African buffalo to restrict mycobacterial growth...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28454654/the-diacylglycerol-acyltransferase-rv3371-of-mycobacterium-tuberculosis-is-required-for-growth-arrest-and-involved-in-stress-induced-cell-wall-alterations
#18
Shivangi Rastogi, Amit Kumar Singh, Gyan Chandra, Pragati Kushwaha, Garima Pant, Kavita Singh, Kalyan Mitra, Koneni V Sashidhara, Manju Y Krishnan
Triacylglycerol (TAG) is important to mycobacteria both as cell envelope component and energy reservoir. Mycobacterium tuberculosis (Mtb) genome encodes at least 15 putative TAG synthase (tgs)s. We report that one of these genes, Rv3371, specific to pathogenic mycobacteria, when expressed in M. smegmatis leads to modifications in colony morphotype, bacterial architecture, cell surface properties and elevated TAG levels. Rv3371 was found to largely localize in the cell membrane. The Rv3371 promoter is minimally active during exponential growth in vitro, however, is up-regulated under stationary phase, hypoxia, nutrient starvation, nitrosative stress, low iron, in IFN-γ activated macrophages and infected mice...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28454653/strains-of-mycobacterium-tuberculosis-transmitting-infection-in-brazilian-households-and-those-associated-with-community-transmission-of-tuberculosis
#19
Solange Alves Vinhas, Edward C Jones-López, Rodrigo Ribeiro Rodrigues, Mary Gaeddert, Renata Lyrio Peres, Patricia Marques-Rodrigues, Paola Poloni Lobo de Aguiar, Laura Forsberg White, David Alland, Padmini Salgame, David Hom, Jerrold J Ellner, Reynaldo Dietze, Lauren F Collins, Elena Shashkina, Barry Kreiswirth, Moisés Palaci
Molecular epidemiologic studies have shown that the dynamics of tuberculosis transmission varies geographically. We sought to determine which strains of Mycobacterium tuberculosis (MTB) were infecting household contacts (HHC), and which were causing clusters of tuberculosis (TB) disease in Vitoria-ES, Brazil. A total of 741 households contacts (445 TST +) and 139 index cases were characterized according to the proportion of contacts in each household that had a tuberculin skin test positive: low (LT) (≤40% TST+), high (HT) (≥70% TST+) and (40-70% TST+) intermediate (IT) transmission...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28454652/selection-characterization-and-application-of-dna-aptamers-for-detection-of-mycobacterium-tuberculosis-secreted-protein-mpt64
#20
Marzhan Sypabekova, Aliya Bekmurzayeva, Ronghui Wang, Yanbin Li, Claude Nogues, Damira Kanayeva
Rapid detection of Mycobacterium tuberculosis (Mtb), an etiological agent of tuberculosis (TB), is important for global control of this disease. Aptamers have emerged as a potential rival for antibodies in therapeutics, diagnostics and biosensing due to their inherent characteristics. The aim of the current study was to select and characterize single-stranded DNA aptamers against MPT64 protein, one of the predominant secreted proteins of Mtb pathogen. Aptamers specific to MPT64 protein were selected in vitro using systematic evolution of ligands through exponential enrichment (SELEX) method...
May 2017: Tuberculosis
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