Tuberculosis RSS feed: Current Issue. Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism. Areas covered include: immunology immunogenetics pathogenetics microbiology microbial physiology pathogenesis pathology molecular epidemiology diagnostics vaccine development drug resistance The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis. To view the benefits of Online Submission please click here. http://www.tuberculosisjournal.com/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Tuberculosis1472-9792904July 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.tuberculosisjournal.com/article/PIIS1472979210000715/abstract?rss=yesEditorial Board10.1016/S1472-9792(10)00071-5Tuberculosis 90, 4 (2010)2010-07-01Tuberculosis2010-07-01904S1472-9792(10)X0005-1iihttp://www.tuberculosisjournal.com/article/PIIS1472979210000624/abstract?rss=yesSummary: The chemotherapy of tuberculous lymphadenopthy, the commonest form of extra-pulmonary tuberculosis, is reviewed and a recommendation made for the treatment of this condition in children. Fifteen papers were identified recording the treatment and follow-up of 1133 adults and children with six-month isoniazid and rifampicin based regimens. In 32 (2.8%) cases treatment was recommenced, but in only one case was relapse microbiologically confirmed and in a further four histology was compatible with tuberculosis. Four studies enrolling 484 adults and children, record the follow-up of patients receiving 6–18 months treatment with INH and RMP based regimens; treatment was recommenced in 24 (5%), but in no case was relapse confirmed microbiologically. Five papers describe the treatment and follow-up of 246 adults and children receiving nine-month INH and RMP based regimens and record the recommencement of treatment in 4 (1.6%) cases, but in no case was relapse confirmed microbiologically. Four controlled studies failed to show any advantage for treatment regimens longer than six months. Paradoxical recurrence and worsening of clinical features was common during and following all regimens being recorded in from 3 to20% of patients. Very seldom were these events accompanied by evidence of culture of Mycobacterium tuberculosis to confirm microbiological failure to respond or relapse. Tuberculous lymphadenopathy in children can be safely treated with six months of INH and RMP with PZA given for the first two months and accompanied by EMB in areas with a high prevalence of drug resistance. Every effort should be made to confirm the diagnosis and possible relapses microbiologically.The chemotherapy of tuberculous lymphadenopathy in childrenP.R. Donald10.1016/j.tube.2010.05.001Tuberculosis 90, 4 (2010)2010-06-03Tuberculosis2010-06-03904S1472-9792(10)X0005-1213224http://www.tuberculosisjournal.com/article/PIIS1472979210000417/abstract?rss=yesSummary: The Tuberculosis Database (TBDB) is an online database providing integrated access to genome sequence, expression data and literature curation for TB. TBDB currently houses genome assemblies for numerous strains of Mycobacterium tuberculosis (MTB) as well assemblies for over 20 strains related to MTB and useful for comparative analysis. TBDB stores pre- and post-publication gene-expression data from M. tuberculosis and its close relatives, including over 3000 MTB microarrays, 95 RT-PCR datasets, 2700 microarrays for human and mouse TB related experiments, and 260 arrays for Streptomyces coelicolor. To enable wide use of these data, TBDB provides a suite of tools for searching, browsing, analyzing, and downloading the data. We provide here an overview of TBDB focusing on recent data releases and enhancements. In particular, we describe the recent release of a Global Genetic Diversity dataset for TB, support for short-read re-sequencing data, new tools for exploring gene expression data in the context of gene regulation, and the integration of a metabolic network reconstruction and BioCyc with TBDB. By integrating a wide range of genomic data with tools for their use, TBDB is a unique platform for both basic science research in TB, as well as research into the discovery and development of TB drugs, vaccines and biomarkers.TB database 2010: Overview and updateJames E. Galagan, Peter Sisk, Christian Stolte, Brian Weiner, Michael Koehrsen, Farrell Wymore, T.B.K. Reddy, Jeremy D. Zucker, Reinhard Engels, Marcel Gellesch, Jeremy Hubble, Heng Jin, Lisa Larson, Maria Mao, Michael Nitzberg, Jared White, Zachariah K. Zachariah, Gavin Sherlock, Catherine A. Ball, Gary K. Schoolnik10.1016/j.tube.2010.03.010Tuberculosis 90, 4 (2010)2010-05-21Tuberculosis2010-05-21904S1472-9792(10)X0005-1225235http://www.tuberculosisjournal.com/article/PIIS1472979210000442/abstract?rss=yesSummary: Mycobacterium tuberculosis has 10 universal stress proteins, whose function is unknown. However, proteomic and transcriptomic analyses have shown that a number of usp genes are significantly upregulated under hypoxic conditions and in response to nitric oxide and carbon monoxide, as well as during M. tuberculosis infection of macrophage cell lines. Six of these USPs are part of the DosR regulon and this, along with their expression pattern and the phenotypes of usp mutants in other bacterial species, suggests a potential role in the persistence and/or intracellular survival of Mtb. Knock-out mutants of individual usp genes encoding the USPs Rv1996, Rv2005c, Rv2026c and Rv2028c were generated and their growth and survival under hypoxic and other stress conditions examined. Although the majority of usp genes are highly induced in hypoxic conditions, mutation did not affect the long term survival of Mtb under these conditions, or in response to a range of stress conditions chosen to represent the environmental onslaughts experienced by the bacillus during an infection, nor during infection of mouse and human – derived macrophage cell lines. The possibility remains that these USPs are functionally redundant in Mtb.Individual Mycobacterium tuberculosis universal stress protein homologues are dispensable in vitroS.M. Hingley-Wilson, K.E.A. Lougheed, K. Ferguson, S. Leiva, H.D. Williams10.1016/j.tube.2010.03.013Tuberculosis 90, 4 (2010)2010-06-14Tuberculosis2010-06-14904S1472-9792(10)X0005-1236244http://www.tuberculosisjournal.com/article/PIIS1472979210000466/abstract?rss=yesSummary: The Mycobacterium tuberculosis protein Rv2377c (71 residues, MW=8.4kDa) has been characterized using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy. Rv2377c was the first identified member of the MbtH-like family of proteins. MbtH-like proteins have been implicated in siderophore biosynthesis, however, their precise biochemical function remain unknown. Size exclusion chromatography and NMR spectroscopy show that Rv2377c is a monomer in solution. Circular dichroism spectroscopy indicates that Rv2377c unfolds upon heating and will reversibly fold into its native conformation upon cooling. Using NMR-based methods the solution structure of Rv2377c was determined and some of the dynamic properties of the protein studied. The protein contains a three-strand, anti-parallel β-sheet (β3:β1:β2) nestled against one C-terminal α-helix (S44–N55). Weak or absent amide cross peaks in the 1H–15N HSQC spectrum for many of the β1 and β2 residues suggest intermediate motion on the ms to μs time scale at the β1:β2 interface. Amide cross peaks in the 1H–15N HSQC spectrum are absent for all but one residue at the C-terminus (W56–D71), a region that includes a highly conserved sequence WXDXR, suggesting this region is intrinsically disordered. The latter observation differs with the crystal structure of another MbtH-like protein, PA2412 from Pseudomonas aeruginosa, where a second ordered α-helix was observed at the extreme C-terminus.Solution structure of Rv2377c-founding member of the MbtH-like protein familyGarry W. Buchko, Chang-Yub Kim, Thomas C. Terwilliger, Peter J. Myler10.1016/j.tube.2010.04.002Tuberculosis 90, 4 (2010)2010-05-03Tuberculosis2010-05-03904S1472-9792(10)X0005-1245251http://www.tuberculosisjournal.com/article/PIIS1472979210000661/abstract?rss=yesSummary: Regulatory T cells (Tregs) play an essential role in immune homeostasis. In infectious diseases Tregs may inhibit protective responses facilitating pathogen multiplication and dissemination, but they may also limit the inflammatory response diminishing tissue damage. Although there is experimental and clinical evidence that Tregs are induced during Mycobacterium tuberculosis infection, their role in the immunopathogenesis of tuberculosis is still not completely understood. In this study, the phenotype, frequency and activity of circulating Tregs in active and latent tuberculosis were evaluated. Phenotypic analysis showed that Tregs were CD4+CD25highFOXP3+CD45RO+CD127-. High levels of circulating Tregs were found in patients with active pulmonary tuberculosis, compared to individuals with latent infection. Treg activity was evaluated by ELISPOT by determining the effect of CD25+ cell depletion on the frequency of IFN-γ and IL-17 producing cells after in vitro stimulation with ESAT-6, CFP-10 and PPD. Treg depletion increased the frequency of IFN-γ producing cells, without affecting the frequency of IL-17 producing cells, in both active and latent tuberculosis, irrespective of the antigen used. Neutralization of IL-10 did not have any effect on the frequency of IFN-γ and IL-17 producing cells. Altogether, these results suggest that during active tuberculosis Tregs inhibit protective Th1 responses, but not the proinflammatory Th17 responses, facilitating mycobacterial replication and tissue damage.Regulatory T cell frequency and modulation of IFN-gamma and IL-17 in active and latent tuberculosisNancy D. Marin, Sara C. París, Viviana M. Vélez, Carlos A. Rojas, Mauricio Rojas, Luis F. García10.1016/j.tube.2010.05.003Tuberculosis 90, 4 (2010)2010-07-01Tuberculosis2010-07-01904S1472-9792(10)X0005-1252261http://www.tuberculosisjournal.com/article/PIIS1472979210000478/abstract?rss=yesSummary: To evaluate the usefulness of the American cotton rat (Sigmodon hispidus) in the evaluation of vaccine-induced resistance, we infected BCG-vaccinated and non-vaccinated cotton rats with Mycobacterium tuberculosis (H37Rv) via the respiratory route. Lung histopathology of these animals showed loose, disorganized granulomas which were non-necrotic up to 8 weeks post-infection. Moreover, we were not able to detect a DTH response after intradermal injection with PPD antigen. Prior BCG vaccination significantly reduced lung and spleen bacterial loads by 1–1.5log CFU and upregulated PPD-induced proliferation and production of IFNγ in lymphocyte cultures. We conclude that pulmonary infection of the cotton rat with Mtb more closely resembles the phenotype seen in mice rather than guinea pigs.BCG vaccination in the cotton rat (Sigmodon hispidus) infected by the pulmonary route with virulent Mycobacterium tuberculosisChristine T. McFarland, Lan Ly, Amminikutty Jeevan, Toshiko Yamamoto, Bradley Weeks, Angelo Izzo, David McMurray10.1016/j.tube.2010.03.014Tuberculosis 90, 4 (2010)2010-05-07Tuberculosis2010-05-07904S1472-9792(10)X0005-1262267http://www.tuberculosisjournal.com/article/PIIS1472979210000636/abstract?rss=yesSummary: Meningeal tuberculosis is a severe type of extrapulmonary disease, which is thought to begin with respiratory infection, followed by hematogenous dissemination and brain infection. Host genetic susceptibility factors and specific mycobacterial substrains could be involved in its development. From an epidemiological study in Colombia, we selected three Mycobacterium tuberculosis clinical strains isolated from the cerebrospinal fluid (CSF) of patients with meningeal tuberculosis, and used them to infect BALB/c mice through the intratracheal route. These strains showed a distinctive spoligotype pattern. The course of infection in terms of strain virulence (mice survival, bacillary loads in lungs), bacilli dissemination and extrapulmonary infection (bacilli loads in blood, brain, liver, kidney and spleen), and immune responses (cytokine expression determined by real time PCR in brain and lung) was studied and compared with that induced by the laboratory strain H37Rv and other five clinical strains isolated from patients with pulmonary TB. All the clinical isolates from meningeal TB patients disseminated extensively through the hematogenous route infecting the brain, producing inflammation in the cerebral parenchyma and meninges, whereas H37Rv and clinical isolates from pulmonary TB patients showed very limited efficiency to infect the brain. Thus, it seems that mycobacterial strains with a distinctive genotype are able to disseminate extensively after the respiratory infection and infect the brain.Specific bacterial genotypes of Mycobacterium tuberculosis cause extensive dissemination and brain infection in an experimental modelRogelio Hernandez Pando, Diana Aguilar, Ingrid Cohen, Martha Guerrero, Wellman Ribon, Patrícia Acosta, Hector Orozco, Brenda Marquina, Citlal Salinas, Daniel Rembao, Clara Espitia10.1016/j.tube.2010.05.002Tuberculosis 90, 4 (2010)2010-06-28Tuberculosis2010-06-28904S1472-9792(10)X0005-1268277