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Mario Alberto Flores-Valdez, Cristian Alfredo Segura-Cerda, Jorge Gaona-Bernal
Effective prevention of tuberculosis (Tb) would undoubtedly be of paramount relevance in the control of its global burden, which resulted in more than 6 million new cases in 2016. Research aimed to improve the current vaccine, Bacillus Calmette- Guérin (BCG), or directed to develop new candidates, has taken into account the interaction between the host and Mycobacterium tuberculosis (Mtb). Recently, autophagy, an intracellular process of the host, has been shown to act as a mechanism that contributes to bacilli clearance in vitro and in vivo...
March 13, 2018: Molecular Immunology
Andrew McDowell, Neeraj Raizada, Sunil D Khaparde, Raghuram Rao, Sanjay Sarin, Aakshi Kalra, Virender Singh Salhotra, Sreenivas Achuthan Nair, Catharina Boehme, Claudia M Denkinger
BACKGROUND: Diagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF ('Xpert')-a rapid molecular assay with high sensitivity and specificity-for pediatric presumptive TB patients, as recommended by India's Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers...
2018: PloS One
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Swati Jaiswal, Kishore K Srivastava
Mycobacterium tuberculosis (MTB) is a successful pathogen which increases persistence inside the host macrophage by subverting its defence mechanism. Mycobacteria regulate the pathogenesis and intracellular survival by controlling its interaction with host protein(s). Galectin 3 is a member of the β-galactoside binding gene family which is involved in several biological functions. In the present study we have expressed the mycobacterial protein tyrosine kinase (PtkA) in the cytosol of host macrophages through a eukaryotic promoter vector and found that it down-regulates Galectin 3...
March 12, 2018: Biochemical and Biophysical Research Communications
Júlia Perera-Bel, Barbara Hutter, Christoph Heining, Annalen Bleckmann, Martina Fröhlich, Stefan Fröhling, Hanno Glimm, Benedikt Brors, Tim Beißbarth
BACKGROUND: A comprehensive understanding of cancer has been furthered with technological improvements and decreasing costs of next-generation sequencing (NGS). However, the complexity of interpreting genomic data is hindering the implementation of high-throughput technologies in the clinical context: increasing evidence on gene-drug interactions complicates the task of assigning clinical significance to genomic variants. METHODS: Here we present a method that automatically matches patient-specific genomic alterations to treatment options...
March 15, 2018: Genome Medicine
Marco Pio La Manna, Valentina Orlando, Paolo Li Donni, Guido Sireci, Paola Di Carlo, Antonio Cascio, Francesco Dieli, Nadia Caccamo
We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells...
2018: PloS One
Bhagya Sudheer, Manisha Agarwal, Deepa Sharma, Ravi Mehta, Kalpana Babu
PURPOSE: To report our experience of using Endobronchial ultrasound-guided transbronchial lymph node aspiration (EBUS-TBNA) in assessing the etiology in uveitis from two tertiary eye-care centers in India. MATERIALS & METHODS: Retrospective interventional case series. RESULTS: A total of 99 patients of uveitis who underwent EBUS-TBNA were included in the study. Mycobacterium tuberculosis (MTb) was detected on culture in 5 cases, 3 cases by polymerase chain reaction and caseating granulomas in 25 cases...
March 15, 2018: Ocular Immunology and Inflammation
Prakash Shrestha, Hemanta Khanal, Prasanna Dahal, Pranita Dongol
Background: In Nepal, introduction of GeneXpert MTB/RIF assay (Xpert assay) as an initial confirmation test for tuberculosis (TB) has been considered to have impact as a significant decrease in number of clinically diagnosed pulmonary tuberculosis (PTB) cases than previous years. This study aims to find out the distribution profile of suspected tuberculosis cases according to patients age, gender, treatment history and HIV status as well as to evaluate the utility of the Xpert assay over conventional acid-fast bacilli (AFB) staining method for the proper diagnosis of M...
2018: Open Microbiology Journal
Víctor Vinuesa, Rafael Borrás, María Luisa Briones, María Ángeles Clari, Vicenta Cresencio, Estela Giménez, Carmen Muñoz, Rosa Oltra, Emilio Servera, Talia Scheelje, Carlos Tornero, David Navarro
The potential impact of routine real-time PCR testing of respiratory specimens from patients with presumptive tuberculosis in terms of diagnostic accuracy and time to tuberculosis treatment inception in low-prevalence settings remains largely unexplored. We conducted a prospective intervention cohort study. Respiratory specimens from 1,020 patients were examined by acid-fast bacilli smear microscopy, tested by the real-time Mycobacterium tuberculosis complex PCR assay (Abbott RealTi me MTB PCR) and cultured in mycobacterial media...
March 14, 2018: Journal of Clinical Microbiology
Yi-Yi Wang, Bing-di Xie
Central nervous system (CNS) disease caused by Mycobacterium tuberculosis (MTB) is highly devastating. Tuberculous meningitis (TBM) is the most common form of CNS tuberculosis (TB). Rapid, sensitive, and affordable diagnostic tests are not available. Ziehl-Neelsen (ZN) stain has a very low sensitivity in cases of TBM, the sensitivity rates is of about 10-20%.The detection rate can be improved by taking large volume CSF samples (>6 ml) and prolonged slide examination (30 min). Culture of MTB from the CSF is slow and insufficiently sensitive...
2018: Methods in Molecular Biology
Wenting He, Shengfeng Hu, Xialin Du, Qian Wen, Xiao-Ping Zhong, Xinying Zhou, Chaoying Zhou, Wenjing Xiong, Yuchi Gao, Shimeng Zhang, Ruining Wang, Jiahui Yang, Li Ma
The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages...
2018: Frontiers in Immunology
Mariateresa Coppola, Susan J F van den Eeden, Naoko Robbins, Louis Wilson, Kees L M C Franken, Linda B Adams, Tom P Gillis, Tom H M Ottenhoff, Annemieke Geluk
Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines...
2018: Frontiers in Immunology
Saeed Rismani Yazi, Reza Nosrati, Corey A Stevens, David Vogel, Carlos Escobedo
Magnetotactic bacteria (MTB) migrate in complex porous sediments where fluid flow is ubiquitous. Here, we demonstrate that magnetotaxis enables MTB to migrate effectively through porous micromodels. Directed MTB can circumvent curved obstacles by traveling along the boundaries and pass flat obstacles by repeatedly switching between forward and backward runs. Magnetotaxis enables directed motion of MTB through heterogeneous porous media, overcoming tortuous flow fields with local velocities as high as 250  μ m s-1 ...
January 2018: Biomicrofluidics
Zhirui Wang, Tong Xie, Cheng Mu, Rui Sun, Chunhua Wang, Hui Zhao, Hanfang Ju
Ofloxacin (OFX) resistant Mycobacterium tuberculosis (MTB) isolates have been increasingly observed worldwide, complicating tuberculosis control. This study investigated the performance of sequencing which could predict OFX resistance in MTB isolates from positive Bactec MGIT 960 cultures. A total of 214 Bactec MGIT 960 positive cultures were identified by p-nitrobenzoic-acid and thiophene-2-carboxylic hydrazide. Drug susceptibility testing was performed using the proportion method and sequencing. The sequence results were compared with the results of the proportion method to analyze the consistency between the results...
January 2018: Annals of Clinical and Laboratory Science
Divya Arora, Yogesh Chawla, Basanti Malakar, Archana Singh, Vinay Kumar Nandicoori
The cell wall of Mycobacterium tuberculosis (Mtb) is a complex structure that protects the pathogen in hostile environments. Peptidoglycan (PG), which helps determine the morphology of the cell envelope, undergoes substantial remodeling under stress. This meshwork of linear chains of sugars, crosslinked through attached peptides, is generated through the sequential action of enzymes termed transglycosylases and transpeptidases. The Mtb genome encodes two classical transglycosylases and four transpeptidases, the functions of which are not fully elucidated...
March 12, 2018: Journal of Biological Chemistry
Sakshi Agarwal, Prabhakar Tiwari, Amar Deep, Saqib Kidwai, Shamba Gupta, Krishan Gopal Thakur, Ramandeep Singh
Toxin-antitoxin (TA) systems are bicistronic genetic modules that are ubiquitously present in bacterial genomes. Mycobacterium tuberculosis (Mtb) genome encodes for 90 putative TA systems and these are considered to be associated with maintenance of bacterial genomic stability or its survival under unfavorable environment. Majority of these in Mtb have been annotated as belonging to the Virulence associated protein B and C (VapBC) family. However, their precise role in bacterial physiology has not been elucidated...
February 24, 2018: Journal of Infectious Diseases
Ankur Gupta-Wright, Gillian S Tomlinson, Molebogeng X Rangaka, Helen A Fletcher
On 24th March, the world commemorates the day in 1882 when Dr Robert Koch announced his discovery of Mycobacterium tuberculosis (MTB). Over 130 years later, tuberculosis (TB) continues to affect individuals, communities, and entire health systems and economies. Koch unsuccessfully tried to 'cure' TB, and despite major advances in other areas of medicine, control of TB remains elusive- in 2016 TB was the leading infectious cause of death. The STOP TB partnership and World Health Organization (WHO) have announced their theme for World TB Day 2018 "Wanted: Leaders for a TB-Free World...
2018: F1000Research
Mehmet Demirci, Suat Saribas, Nigar Ozer, Sezer Toprak, Emel Caglar, Gonenc Ortakoylu, Pelin Yuksel, Gulsel Ayaz, Hrisi Bahar Tokman, Omer Uysal, Harika Oyku Dinc, Tevhide Ziver, Bekir Kocazeybek
BACKGROUND: Several nucleic acid amplification techniques (IS6110, 16S rRNA, and 85B mRNA) were developed for the rapid, direct detection of Mycobacterium tuberculosis. We aimed to assess the diagnostic performance of 85B mRNA-based RT-qPCR by comparing with the real-time PCR COBAS TaqMan MTB Kit while using the BACTEC MGIT 960 method as the gold standard. METHODS: 60 patients with confirmed pulmonary TB and 60 individuals without TB were included as the study and control groups, respectively...
March 8, 2018: Journal of Infection and Public Health
Céline Rens, Françoise Laval, Ruddy Wattiez, Philippe Lefèvre, François Dufrasne, Mamadou Daffé, Véronique Fontaine
The multiplicity of drug resistant Mycobacterium tuberculosis (Mtb) strains is a growing health issue. New therapies are needed, acting on new targets. The I3-Ag85 was already reported to reduce the amount of trehalose dimycolate lipid of the mycobacterial cell wall. This inhibitor of Ag85C increased the mycobacterial wall permeability. We previously showed that M. tuberculosis strains, even multi-drug resistant and extensively-drug resistant strains, can be susceptible to vancomycin when concomitantly treated with a drug altering the cell envelope integrity...
January 2018: Tuberculosis
Sunil Kumar, Rukmankesh Mehra, Sumit Sharma, Naveen Prakash Bokolia, Diksha Raina, Amit Nargotra, Parvinder Pal Singh, Inshad Ali Khan
A limited number of anti-tuberculosis drug candidates with novel mode of action have entered clinical trials in recent years. ATP synthase is one such validated drug target which has yielded a drug recently. The aim of this study was to identify the novel chemical scaffolds targeting the Mycobacterium tuberculosis (M. tuberculosis) ATP synthase. In this study, inverted membrane vesicles of Mycobacterium smegmatis were prepared to establish luciferin based ATP estimation assay. This assay was used to screen 700 compounds which were earlier found to be active on the whole cell of M...
January 2018: Tuberculosis
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