The host microbiome and impact of tuberculosis chemotherapy
The treatment of Mycobacterium tuberculosis infection is often viewed in isolation from other human microbial symbionts. Understandably, the clinical priority is eliminating active or latent tuberculosis (TB) in patients. With the increasing resolution of molecular biology technologies, it is becoming apparent that antibiotic treatment can perturb the homeostasis of the host microbiome. For example, dysbiosis of the gut microbiota has been associated with an increased risk of the development of asthma, obesity and diabetes. (Source: Tuberculosis)
Source: Tuberculosis - September 1, 2018 Category: Respiratory Medicine Authors: Ronan F. O'Toole, Sanjay S. Gautam Tags: Review Source Type: research
Uncloaking an ancient adversary: Can pathogen biomarker elicitors play a role in confirming extrapulmonary TB and latent TB infection?
Latent tuberculosis infection (LTBI) is diagnosed immunologically using the Mantoux tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). While widely used, immunodiagnostics can produce false negative or false positive results. Pathogen biomarkers provide an alternative, but direct detection in LTBI and extrapulmonary TB cases is challenging. Mycobacterium tuberculosis grows slowly, has limited hematogenous movement, is protected by a lipid rich cell wall, and produces low levels of secreted factors. (Source: Tuberculosis)
Source: Tuberculosis - August 31, 2018 Category: Respiratory Medicine Authors: Brad W. Porter, Thara K. Venkatappa Tags: Review Source Type: research
Integrated analysis of ethionamide resistance loci in Mycobacterium tuberculosis clinical isolates
Tuberculosis patients taking second line drugs such as ethionamide (ETH) have often experienced previous treatment failure and usually have a complex history of disease and treatment that can span decades. Mutations in the ETH activating enzyme, EthA, confer resistance through undescribed mechanisms. To explore the impact of EthA mutations on ETH resistance, data from a total of 160 ETHR isolates was analysed. The most frequently mutated positions are within regions that display sequence conservation with the active site of OTEMO, another FAD-containing NADH-binding Baeyer-Villiger monooxygenase (BVMO), or with the sugar b...
Source: Tuberculosis - August 26, 2018 Category: Respiratory Medicine Authors: Duanne Alves da Silva, Nicole Victor Ferreira, Amanda Mendes Rego, Pamela Chrystina Pinto Barbosa, Rodrigo Fernandes Machado, Alessandra Pimentel, Lusiano Motta dos Reis, Lucindo Cardoso de Pina, Paulo Redner, Paulo Cesar de Souza Caldas, F átima Cristin Tags: Drug Discovery and Resistance Source Type: research
Cytokine biomarkers for the diagnosis of tuberculosis infection and disease in adults in a low prevalence setting
This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. (Source: Tuberculosis)
Source: Tuberculosis - August 25, 2018 Category: Respiratory Medicine Authors: Vanessa Clifford, Marc Tebruegge, Christel Zufferey, Susie Germano, Ben Forbes, Lucy Cosentino, Elizabeth Matchett, Emma McBryde, Damon Eisen, Roy Robins-Browne, Alan Street, Justin Denholm, Nigel Curtis Tags: Diagnostics Source Type: research
Meeting report: 5th Global Forum on TB vaccines, 20-23 February 2018, New Delhi India
The 5th Global Forum on TB Vaccines was held in New Delhi, India from 20-23 February 2018. This was the largest Global Forum on TB Vaccines to date with nearly 350 participants from more than 30 countries. The program included over 60 speakers in 12 special, plenary and breakout sessions and 72 posters. This Global Forum brought a great sense of momentum and excitement to the field. New vaccines are in clinical trials, new routes of delivery are being tested, novel assays and biomarker signatures are being developed, and the results from the first prevention of infection clinical trial with the H4:IC31 vaccine candidate an...
Source: Tuberculosis - August 24, 2018 Category: Respiratory Medicine Authors: Krishnamohan Atmakuri, Adam Penn-Nicholson, Rachel Tanner, Hazel M. Dockrell Tags: Review Source Type: research
Improvement of the resistance against early Mycobacterium tuberculosis-infection in the absence of PI3K γ enzyme is associated with increase of CD4+IL-17+ cells and neutrophils
Given the impossibility to study the lung immune response during Mycobacterium tuberculosis-latent infection, and consequently, the mechanisms that control the bacterial load, it is reasonable to determine the activation of local immunity in the early phase of the infection. The phosphatidylinositol-3-kinase gamma enzyme (PI3K γ) is involved in the leukocyte recruitment, phagocytosis and cellular differentiation, and therefore, it is considered a promising target for the development of immunotherapies for chronic inflammatory diseases. (Source: Tuberculosis)
Source: Tuberculosis - August 23, 2018 Category: Respiratory Medicine Authors: M.P. Cavalcanti-Neto, R.Q. Prado, A.R. Pi ñeros, C.A. Sérgio, T.B. Bertolini, A.F. Gembre, S.G. Ramos, V.L. Bonato Tags: Immunological Aspects Source Type: research
BCG constitutively expressing the adenylyl cyclase encoded by Rv2212 increases its immunogenicity and reduces replication of M. tuberculosis in lungs of BALB/c mice
Mycobacterium tuberculosis remains as a threat to public health around the world with 1.7 million cases of TB-associated deaths during 2016. Despite the use of Bacillus Calmette-Guerin (BCG) vaccine, control of the infection has not been successful. Because of this, several efforts have been made in order to develop new vaccines capable of boosting or attempted for replacing current BCG. We previously showed that over expression of the M. tuberculosis adenylyl cyclase encoding gene Rv2212 in BCG bacilli (BCG-Rv2212), induced an attenuated phenotype when administered in BALB/c mice. (Source: Tuberculosis)
Source: Tuberculosis - August 23, 2018 Category: Respiratory Medicine Authors: C ésar Pedroza-Roldán, Brenda Marquina-Castillo, Dulce Mata-Espinosa, Jorge Barrios-Payán, Michel de Jesús Aceves-Sánchez, Rogelio Hernández Pando, Mario Alberto Flores-Valdez Tags: Model Systems Source Type: research
Diagnostic evaluation of an in-house developed single-tube, duplex, nested IS6110 real-time PCR assay for rapid pulmonary tuberculosis diagnosis
To perform a prospective evaluation on the diagnostic performance of an in-house developed, duplex nested IS6110 real-time Polymerase-Chain-Reaction (PCR) assay (IS6110-qPCR assay) for rapid pulmonary TB diagnosis. (Source: Tuberculosis)
Source: Tuberculosis - August 22, 2018 Category: Respiratory Medicine Authors: Kenneth Siu-Sing Leung, Gilman Kit-Hang Siu, Kingsley King-Gee Tam, Pak-Leung Ho, Samson Sai-Yin Wong, Eunice Ka-Chun Leung, Shi Hui Yu, Oliver Chiu-Kit Ma, Wing-Cheong Yam Tags: Diagnostics Source Type: research
Diabetes screen during tuberculosis contact investigations highlights opportunity for new diabetes diagnosis and reveals metabolic differences between ethnic groups
Type 2 diabetes (T2D) is a prevalent risk factor for tuberculosis (TB), but most studies on TB-T2D have focused on TB patients, been limited to one community, and shown a variable impact of T2D on TB risk or treatment outcomes. We conducted a cross-sectional assessment of sociodemographic and metabolic factors in adult TB contacts with T2D (versus no T2D), from the Texas-Mexico border to study Hispanics, and in Cape Town to study South African Coloured ethnicities. The prevalence of T2D was 30.2% in Texas-Mexico and 17.4% in South Africa, with new diagnosis in 34.4% and 43.9%, respectively. (Source: Tuberculosis)
Source: Tuberculosis - August 18, 2018 Category: Respiratory Medicine Authors: Blanca I. Restrepo, L éanie Kleynhans, Alejandra B. Salinas, Bassent Abdelbary, Happy Tshivhula, Genesis P. Aguillón-Durán, Carine Kunsevi-Kilola, Gloria Salinas, Kim Stanley, Stephanus T. Malherbe, Elizna Maasdorp, Moncerrato Garcia-Viveros, Ilze Louw Tags: Epidemiology Source Type: research
Diagnostic performance of GM-CSF and IL-2 in response to long-term specific-antigen cell stimulation in patients with active and latent tuberculosis infection
A simple blood test for detecting active tuberculosis (TB) could be key to this epidemic containment, given that a large proportion of patients are unable to produce sputum for testing. Currently available interferon- γ release assays (IGRAs) are inadequate to diagnose active TB, with reported pooled sensitivity and specificity both under 81%. (Source: Tuberculosis)
Source: Tuberculosis - August 13, 2018 Category: Respiratory Medicine Authors: Mar ía Elvira Balcells, Cinthya Ruiz-Tagle, Camila Tiznado, Patricia García, Rodrigo Naves Tags: Diagnostics Source Type: research
The EU approved antimalarial pyronaridine shows antitubercular activity and synergy with rifampicin, targeting RNA polymerase
In this study, we have focused on the European Union-approved antimalarial pyronaridine which was found to have in vitro activity against Mycobacterium tuberculosis (MIC 5 μg/mL). In macromolecular synthesis assays, pyronaridine resulted in a severe decrease in incorporation of 14C-uracil and 14C-leucine similar to the effect of rifampicin, a known inhibitor of M. tuberculosis RNA polymerase. (Source: Tuberculosis)
Source: Tuberculosis - August 11, 2018 Category: Respiratory Medicine Authors: Giorgia Mori, Beatrice Silvia Orena, Clara Franch, Lesley A. Mitchenall, Adwait Anand Godbole, Liliana Rodrigues, Clara Aguilar-P érez, Júlia Zemanová, Stanislav Huszár, Martin Forbak, Thomas R. Lane, Mohamad Sabbah, Nathalie Deboosere, Rosangela Frit Tags: Drug Discovery and Resistance Source Type: research
In silico designing of domain B selective gyrase inhibitors for effective treatment of resistant tuberculosis
One of the major mechanisms followed by the therapeutic agents to target the causative organism of TB, Mycobacterium tuberculosis, involves disruption of its DNA replication cycle. The process of replication involves two steps, i.e., breakage and reunion of DNA at gyrase A (GyrA) domain and ATP hydrolysis at gyrase B (GyrB) domain, both occur simultaneously. Current therapy for multi-drug resistant TB (MDR-TB) involves FDA approved, fluoroquinolone-based antibiotics, which act by targeting replication process at GyrA domain. (Source: Tuberculosis)
Source: Tuberculosis - August 8, 2018 Category: Respiratory Medicine Authors: Aanchal Kashyap, Pankaj Kumar Singh, Om Silakari Source Type: research
Genetic diversity of Mycobacterium tuberculosis complex isolates circulating in an area with high tuberculosis incidence: Using 24-locus MIRU-VNTR method
We aimed to determine the genetic diversity, phylogenetic relationship and transmission dynamics of Mycobacterium tuberculosis complex (MTBC) genotypes in an area with high tuberculosis (TB) incidence. A set of 164 MTBC isolates from new TB patients of Golestan province, Iran were subjected to genotyping using the standard 24-locus MIRU-VNTR method. Recent TB transmission was evaluated and phylogenetic relationships were analysed by minimum spanning tree and cluster-graph methods. Among the 164 isolates, 132 distinct patterns were detected. (Source: Tuberculosis)
Source: Tuberculosis - August 6, 2018 Category: Respiratory Medicine Authors: Noormohamad Mansoori, Mehdi Yaseri, Farzam Vaziri, Masoumeh Douraghi Tags: Epidemiology Source Type: research
Novel MprA binding motifs in the phoP regulatory region in Mycobacterium tuberculosis
In this study, we found that the response regulator MprA can bind to the phoP promoter. Four repeat motifs, D1-D4, constituting two predicted binding sites, were located in the region protected by MprA in DNA footprinting. (Source: Tuberculosis)
Source: Tuberculosis - August 3, 2018 Category: Respiratory Medicine Authors: Peipei Zhang, Jiafang Fu, Gongli Zong, Meng Liu, Xiuhua Pang, Guangxiang Cao Tags: Molecular Aspects Source Type: research
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide
We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid. (Source: Tuberculosis)
Source: Tuberculosis - August 2, 2018 Category: Respiratory Medicine Authors: Jorgelina J. Franceschelli, Juan M. Belardinelli, Ping Tong, Brendan Loftus, Alejandro Recio-Balsells, Guillermo R. Labadi é, Stephen V. Gordon, Hector R. Morbidoni Tags: Drug Discovery and Resistance Source Type: research
