Host blood RNA signatures predict the outcome of tuberculosis treatment
Biomarkers for tuberculosis treatment outcome will assist in guiding individualized treatment and evaluation of new therapies. To identify candidate biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment cohort was performed. Application of a validated transcriptional correlate of risk for TB revealed symmetry in host gene expression during progression from latent TB infection to active TB disease and resolution of disease during treatment, including return to control levels after drug therapy. (Source: Tuberculosis)
Source: Tuberculosis - August 11, 2017 Category: Respiratory Medicine Authors: Ethan G. Thompson, Ying Du, Stephanus T. Malherbe, Smitha Shankar, Jackie Braun, Joe Valvo, Katharina Ronacher, Gerard Tromp, David L. Tabb, David Alland, Shubhada Shenai, Laura E. Via, James Warwick, Alan Aderem, Thomas J. Scriba, Jill Winter, Gerhard Wa Source Type: research

Editorial Board
(Source: Tuberculosis)
Source: Tuberculosis - August 10, 2017 Category: Respiratory Medicine Source Type: research

Detection of mycobacterial infection in non-human primates using the Xpert MTB/RIF molecular assay
Tuberculosis is a major public health concern, and diagnostic strategies applied to animal populations are scarce. As part of ongoing efforts to control tuberculosis dissemination at our animal facility, two non-human primates (NHP, Saimiri sciureus) presenting cutaneous lesions were examined for mycobacterial infection. Both animals tested positive for acid-fast bacilli and Mycobacterium tuberculosis using a molecular assay (IS6110 PCR). Animals were euthanized and several samples were tested for M. (Source: Tuberculosis)
Source: Tuberculosis - August 10, 2017 Category: Respiratory Medicine Authors: Duanne Alves da Silva, Amanda M. R êgo, Nicole V. Ferreira, Manoela A.S. de Andrade, Aline R. Campelo, Paulo César S. Caldas, Márcia Aparecida S. Pereira, Paulo Redner, Lucindo C. de Pina, Felipe C. Resende, Thalita A. Pissinatti, Claudia A.A. Lopes, T Source Type: research

Whole genome sequencing of clinical strains of Mycobacterium tuberculosis from Mumbai, India: A potential tool for determining drug-resistance and strain lineage
Amplification of drug resistance in Mycobacterium tuberculosis (M.tb) and its transmission are significant barriers in controlling tuberculosis (TB) globally. Diagnostic inaccuracies and delays impede appropriate drug administration, which exacerbates primary and secondary drug resistance. Increasing affordability of whole genome sequencing (WGS) and exhaustive cataloguing of drug resistance mutations is poised to revolutionise TB diagnostics and facilitate personalized drug therapy. However, application of WGS for diagnostics in high endemic areas is yet to be demonstrated. (Source: Tuberculosis)
Source: Tuberculosis - August 9, 2017 Category: Respiratory Medicine Authors: Anirvan Chatterjee, Kayzad Nilgiriwala, Dhananjaya Saranath, Camilla Rodrigues, Nerges Mistry Tags: Diagnostics Source Type: research

Genomic plasticity between human and mycobacterial DNA: A review
Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA. (Source: Tuberculosis)
Source: Tuberculosis - August 8, 2017 Category: Respiratory Medicine Authors: Lawal Danjuma, Mok Pooi Ling, Rukman Awang Hamat, Akon Higuchi, Abdullah A. Alarfaj, Marlina, Giovanni Benelli, Palanisamy Arulselvan, Mariappan Rajan, Suresh Kumar Subbiah Tags: Review Source Type: research

MmpS5/MmpL5 as an efflux pump in Mycobacterium species
Tuberculosis remains an important cause of morbidity and mortality throughout the world, amplified by the expansion of antibiotic resistance. Increasing active efflux of the antibiotic is one of the several strategies used by bacteria to resist to antibiotics. After showing the importance of the RND superfamily of efflux pumps in drug resistance, this review focuses on the protein MmpL5, a transmembrane transporter of Mycobacterium. These exporters should be involved in the variety of roles in bacterial cells, including expelling various drugs. (Source: Tuberculosis)
Source: Tuberculosis - August 4, 2017 Category: Respiratory Medicine Authors: Julien Briffotaux, Wei Huang, Xinwei Wang, Brigitte Gicquel Tags: Review Source Type: research

Single nucleotide polymorphisms in efflux pumps genes in extensively drug resistant Mycobacterium tuberculosis isolates from Pakistan
It is challenging to understand mechanisms of drug resistance in Mycobacterium tuberculosis (MTB) due to the large variability in resistance associated genes. Efflux pump genes contribute to drug resistance and thus add to this complexity. Efflux pumps gene protein superfamilies have been characterized by genome analysis of drug resistant strains and through in vitro transcriptional studies. However, there is limited information regarding efflux pump genes in extensively drug resistant (XDR) tuberculosis (TB) isolates. (Source: Tuberculosis)
Source: Tuberculosis - August 3, 2017 Category: Respiratory Medicine Authors: Akbar Kanji, Rumina Hasan, Asho Ali, Ambreen Zaver, Ying Zhang, Kehkashan Imtiaz, Wanliang Shi, Taane G. Clark, Ruth McNerney, Shoaib Rao, Samreen Shafiq, Zahra Hasan Tags: Drug Discovery and Resistance Source Type: research

Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants
Interferon gamma release assays (IGRAs) have been widely used to diagnose Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate between active TB patients and latent TB infection (LTBI), and the sensitivity of IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in MTB antigen-stimulated and -unstimulated plasma samples to identify host biomarkers that are associated with active TB and MTB infection. Active TB patients, subjects with LTBI and healthy participants were recruited. (Source: Tuberculosis)
Source: Tuberculosis - August 3, 2017 Category: Respiratory Medicine Authors: Xiangyang Yao, Yongliang Liu, Yang Liu, Wei Liu, Zhizhong Ye, Chao Zheng, Shengxiang Ge Tags: Diagnostics Source Type: research

CTL immunogenicity of Rv3615c antigen and diagnostic performances of an ESAT-6/CFP-10/Rv3615c antigen cocktail for Mycobacterium tuberculosis infection
T cell immune responses have played pivotal roles in host immune protection against Mycobacterium tuberculosis (MTB) infection. MTB specific antigen, Rv3615c (EspC), was identified to be as immunodominant as the well-known ESAT-6 and CFP-10, and has brought promising expectations to a more sensitive T-cell based diagnosis and vaccine development. However, limited knowledge about the immunogenicity and diagnostic values of this antigen has restricted its application in clinical practice. Herein, the Rv3615c antigen was identified as a robust CTL immunoantigen with broadly cross-human leucocyte antigen allele recognized pept...
Source: Tuberculosis - August 2, 2017 Category: Respiratory Medicine Authors: Shuguang Tan, Nan Lin, Mingxiang Huang, Qing Wang, Yunhong Tan, Bingxi Li, Ning Zhang, Tianling Guo, Yingbin Cui, Xinchao Chen, Dongping Wang, Jue Wang, Haixia Xiao, William J. Liu, Jinghua Yan, Catherine W.-H. Zhang, Cui Hua Liu, Kanglin Wan, George F. G Tags: Immunological Aspects Source Type: research

Applied multiplex allele specific PCR to detect second-line drug resistance among multidrug-resistant tuberculosis in China
In this study, we applied a multiplex allele-specific PCR (MAS-PCR) to identify the mutations on codons 90 and 94 of gyrA and nucleotide 1401 of rrs for detecting ofloxacin (OFX) and kanamycin (KAN) resistance in 139 MDR-TB isolates from China. Using the traditional phenotypic method as the reference, MAS-PCR detected resistance to OFX and KAN with sensitivities of 67.3% and 76.5%, respectively, and specificities of 100.0%. (Source: Tuberculosis)
Source: Tuberculosis - August 1, 2017 Category: Respiratory Medicine Authors: Ya-ping Liang, Yan Chen, Tong-yang Xiao, Qiang Xia, Hai-can Liu, Xiu-qin Zhao, Chun-yan Zeng, Li-li Zhao, Kang-lin Wan Source Type: research

Mycobacterium tuberculosis sigE mutant ST28 used as a vaccine induces protective immunity in the guinea pig model
With more than 9 million new infections and 1.5 million deaths claimed every year, tuberculosis remains one of the major scourges of humankind. The only vaccine available against this disease, the attenuated strain Mycobacterium bovis, BCG is effective against severe forms of the disease in infants, but scarcely effective in protecting adults from the pulmonary form of the disease, thus not stopping transmission. Consequently, the development of an effective anti-tuberculosis vaccine is a major goal for improving global health. (Source: Tuberculosis)
Source: Tuberculosis - July 24, 2017 Category: Respiratory Medicine Authors: JoLynn Troudt, Elizabeth Creissen, Linda Izzo, Helle Bielefeldt-Ohmann, Stefano Casonato, Riccardo Manganelli, Angelo A. Izzo Source Type: research

A mycobacterial growth inhibition assay (MGIA) for bovine TB vaccine development
Human tuberculosis remains a significant cause of mortality and morbidity throughout the world. The global economic impact of bovine TB is considerable. An effective vaccine would be the most cost-effective way to control both epidemics, particularly in emerging economies. TB vaccine research would benefit from the identification of an immune correlate of protection with which vaccines could be gated at both preclinical and clinical levels. In-vitro mycobacterial growth inhibition assays (MGIA) are functional assays that include most aspects of the complex host immune response to mycobacteria, and they may serve as functio...
Source: Tuberculosis - July 22, 2017 Category: Respiratory Medicine Authors: Ilaria Pepponi, Bhagwati Khatri, Rachel Tanner, Bernardo Villarreal-Ramos, Martin Vordermeier, Helen McShane Source Type: research

Edoardo Maragliano (1849 –1940): The unfortunate fate of a real pioneer in the fight against tuberculosis
At the beginning of the bacteriological era, and the contemporary development of new medical sciences, as biochemistry and cellular pathology, the discovery of Mycobacterium tuberculosis as the causal agent of one of the worst diseases in the world, by R. Koch, in 1882, is considered the starting point of therapeutic and preventive research against tuberculosis. After the first ineffective use of tuberculin as a therapeutic agent, in Italy a group of medical researchers, led by Edoardo Maragliano, full professor of internal medicine at the University of Genoa, initiated experimental and clinical studies to identify therape...
Source: Tuberculosis - July 19, 2017 Category: Respiratory Medicine Authors: Filippo Paluan, Mariano Martini Source Type: research

Exploring the potential of T7 bacteriophage protein Gp2 as a novel inhibitor of mycobacterial RNA polymerase
Over the past six decades, there has been a decline in novel therapies to treat tuberculosis, while the causative agent of this disease has become increasingly resistant to current treatment regimens. Bacteriophages (phages) are able to kill bacterial cells and understanding this process could lead to novel insights for the treatment of mycobacterial infections. Phages inhibit bacterial gene transcription through phage-encoded proteins which bind to RNA polymerase (RNAP), thereby preventing bacterial transcription. (Source: Tuberculosis)
Source: Tuberculosis - July 17, 2017 Category: Respiratory Medicine Authors: J. du Plessis, R. Cloete, L. Burchell, P. Sarkar, R.M. Warren, A. Christoffels, S. Wigneshweraraj, S.L. Sampson Tags: Drug Discovery and Resistance Source Type: research

lysX gene is differentially expressed among Mycobacterium tuberculosis strains with different levels of virulence
Antimicrobial peptides (AMPs) are mainly produced by epithelial cells and macrophages to eliminate infecting mycobacteria through direct antimicrobial activity and immunomodulation. Indeed, it has been described that this line of defense is essential to control infection. However, Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid AMPs activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the present study, we determined that lysX gene is differentially expressed among Mtb strains. (Source: Tuberculosis)
Source: Tuberculosis - July 17, 2017 Category: Respiratory Medicine Authors: Alejandra Montoya-Rosales, Roberta Provvedi, Flor Torres-Juarez, Jose A. Enciso-Moreno, Rogelio Hernandez-Pando, Riccardo Manganelli, Bruno Rivas-Santiago Tags: Mechanisms of Pathogenesis Source Type: research