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https://www.readbyqxmd.com/read/28087649/identification-of-unique-essential-proteins-from-a-m-tuberculosis-f15-lam4-kzn-phage-secretome-library
#1
Thamsanqa Emmanuel Chiliza, Manormoney Pillay, Balakrishna Pillay
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis disease (TB), the leading cause of death from bacterial infection worldwide. Although treatable, the resurgence of multi- and extensively-drug resistance TB is a major setback for the fight against TB globally. Consequently, there is an urgent need for new Mtb derived biomarkers for use in the design of new drugs and rapid point-of-care diagnostic or prognostic tools for management of TB transmission. Therefore, the present study aimed to identify unique Mtb secreted proteins from the extensively drug resistant Mtb F15/LAM4/KZN phage secretome library...
January 12, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28071975/dynamics-of-fluoroquinolones-induced-resistance-in-dna-gyrase-of-mycobacterium-tuberculosis
#2
Bharati Pandey, Sonam Grover, Chetna Tyagi, Sukriti Goyal, Salma Jamal, Aditi Singh, Jagdeep Kaur, Abhinav Grover
DNA gyrase is a validated target of fluoroquinolones which are key components of multidrug resistance (MDR) TB treatment. Most frequent occurring mutations associated with high level of resistance to fluoroquinolone in clinical isolates of TB patients are A90V, D94G and A90V-D94G (double mutant), present in the larger subunit of DNA Gyrase. In order to explicate the molecular mechanism of drug resistance corresponding to these mutations, molecular dynamics and mechanics approach was applied. Structure based molecular docking of complex comprised of DNA bound with Gyrase A (large subunit) and Gyrase C (small subunit) with moxifloxacin revealed high binding affinity to wild type with considerably high Glide XP docking score of -7...
January 10, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28071726/the-ppe2-protein-of-mycobacterium-tuberculosis-translocates-to-host-nucleus-and-inhibits-nitric-oxide-production
#3
Khalid Hussain Bhat, Shruti Srivastava, Sandeep Kumar Kotturu, Sudip Ghosh, Sangita Mukhopadhyay
Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070534/design-and-construction-of-a-cloning-vector-containing-the-hspx-gene-of-mycobacterium-tuberculosis
#4
Yaghoubi Atieh, Aryan Ehsan, Zare Hosna, Alami Shadi, Teimourpour Roghayeh, Meshkat Zahra
BACKGROUND: Tuberculosis (TB) is a major cause of death worldwide. Finding an effective vaccine against TB is the best way to control it. Several vaccines against this disease have been developed but none are completely protective. The aim of this study was to design and construct a cloning vector containing the Mycobacterium tuberculosis (M. tuberculosis) heat shock protein X (hspX). METHODS: First, an hspX fragment was amplified by PCR and cloned into plasmid pcDNA3...
October 2016: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28046053/human-and-mouse-hematopoietic-stem-cells-are-a-depot-for-dormant-mycobacterium-tuberculosis
#5
Julia Tornack, Stephen T Reece, Wolfgang M Bauer, Alexis Vogelzang, Silke Bandermann, Ulrike Zedler, Georg Stingl, Stefan H E Kaufmann, Fritz Melchers
An estimated third of the world's population is latently infected with Mycobacterium tuberculosis (Mtb), with no clinical signs of tuberculosis (TB), but lifelong risk of reactivation to active disease. The niches of persisting bacteria during latent TB infection remain unclear. We detect Mtb DNA in peripheral blood selectively in long-term repopulating pluripotent hematopoietic stem cells (LT-pHSCs) as well as in mesenchymal stem cells from latently infected human donors. In mice infected with low numbers of Mtb, that do not develop active disease we, again, find LT-pHSCs selectively infected with Mtb...
2017: PloS One
https://www.readbyqxmd.com/read/28043637/importance-of-the-%C3%AE-10-helix-for-devr-activation-a-road-map-for-screening-inhibitors-against-devr-mediated-dormancy-of-mycobacterium-tuberculosis
#6
Atul Vashist, D Prithvi Raj, Umesh Datta Gupta, Rajiv Bhat, Jaya Sivaswami Tyagi
OBJECTIVE/BACKGROUND: Bacterial persistence is the hallmark of tuberculosis (TB) and poses the biggest threat to the success of any antitubercular drug regimen. The DevR/DosR dormancy regulator of Mycobacterium tuberculosis belongs to the NarL subfamily of response regulators and is essential for M. tuberculosis persistence in macaque models of TB. The DevR/DosR crystal structure revealed a unique (αβ)4 topology instead of the classical (αβ)5 structure found in the receiver domain of other regulators in this subfamily...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043633/development-of-escherichia-coli-and-mycobacterium-smegmatis-recombinants-expressing-major-mycobacterium-tuberculosis-specific-antigenic-proteins
#7
Hanady A Amoudy, Hussain A Safar, Abu S Mustafa
OBJECTIVE/BACKGROUND: Mycobacterium tuberculosis is an obligate pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most tuberculosis (TB) cases. Until today, the only approved TB vaccine is Bacille Calmette Guerin (BCG), which has been used since 1921. While BCG provides fairly effective protection for infants and young children, its efficacy in adults is variable around the world. This could be due to several parameters including strains of the vaccine and exposure of individuals to different environmental bacterial infections...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043616/whole-genome-sequencing-as-the-ultimate-tool-to-diagnose-tuberculosis
#8
Dick van Soolingen, Rana Jajou, Arnout Mulder, Han de Neeling
In the past two decades, DNA techniques have been increasingly used in the laboratory diagnosis of tuberculosis (TB). The (sub) species of the Mycobacterium tuberculosis complex are usually identified using reverse line blot techniques. The resistance is predicted by the detection of mutations in genes associated with resistance. Nevertheless, all cases are still subjected to cumbersome phenotypic resistance testing. The production of a strain-characteristic DNA fingerprint, to investigate the epidemiology of TB, is done by the 24-locus variable number tandem repeat (VNTR) typing...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043606/ethambutol-resistance-testing-by-mutation-detection-using-mtbdrsl
#9
H Margaryan, S Rüsch-Gerdes, A Hayrapetyan, A Mirzoyan
AIMS AND OBJECTIVES: Despite the successes in managing drug-susceptible TB, drug-resistant (DR) tuberculosis is a major challenge to the effectiveness of National Tuberculosis Program in Armenia, placing the country in the list of 18 high-burden countries for MDR-TB in the WHO European Region. Estimated burden of MDR-TB in 2012 was 9.4 (7-12) and 43 (38-49) among retreatment TB cases. A total of 92 laboratory confirmed cases had been reported to the WHO (57 new and 35 previously treated) out of 511 cases tested for MDR-TB...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043601/best-approaches-to-drug-resistance-surveillance-at-the-country-level
#10
A M Cabibbe, D M Cirillo
In 2014, the World Health Organization (WHO) recommendation to include the endorsed rapid molecular technologies (Xpert MTB/RIF, line probe assays) into surveillance systems and surveys allowed the testing of more tuberculosis (TB) patients for drug resistance at country level than ever before. The whole genome sequencing (WGS) approach is emerging as a more powerful tool for epidemiological and drug-resistant routine surveillances, promising a rapid and simultaneous screening of all the clinically-relevant mutations for the determination of resistance to the first-, second-line, and new anti-TB drugs...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043598/investigation-of-isoniazid-and-ethionamide-cross-resistance-by-whole-genome-sequencing-and-association-with-poor-treatment-outcomes-of-multidrug-resistant-tuberculosis-patients-in-south-africa
#11
L Malinga, J Brand, C Jansen van Rensburg, G Cassell, M van der Walt
OBJECTIVE/BACKGROUND: Ethionamide (ETH) and isoniazid (INH) are part of the backbone regimen used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Both ETH and INH are structurally similar and are activated by ethA and katG gene products. Resistance to INH among MDR-TB patients may cause ETH to be ineffective, as both target nicotinamide adenine dinucleotide-dependent enoyl-acyl carrier protein reductase inhA protein and mutations within inhA gene may lead to their cross-resistance...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043597/impact-of-genotypic-and-phenotypic-resistance-to-second-line-anti-tuberculosis-drugs-on-treatment-outcomes-in-multidrug-resistant-tuberculosis-in-china
#12
Yi Hu, Xubin Zheng, Zhu Ning, Qun Li, Zhengdong Zhang, Sven Hoffner
BACKGROUND: Despite the strong association between drug resistance and genetic mutations, the value of molecular diagnosis of drug resistance to guide the treatment of multidrug-resistant tuberculosis (MDR-TB) remains unclear. This is particularly relevant in resource-limited areas, in which it is difficult to implement the drug susceptibility test. Here, we focused on the association of drug susceptibility phenotype and genotype with treatment outcomes in patients with MDR-TB. METHODS: In a prospective cohort study, we enrolled 252 consecutive patients with confirmed MDR-TB between 2010 and 2013, and outcomes were followed-up over the 24-month treatment course in terms of clinical manifestation and sputum conversion...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043590/use-of-wgs-in-mycobacterium-tuberculosis-routine-diagnosis
#13
Daniela M Cirillo, Andrea M Cabibbe, Maria Rosaria De Filippo, Alberto Trovato, Tullia Simonetti, Gian Maria Rossolini, Enrico Tortoli
OBJECTIVE/BACKGROUND: Whole Genome Sequencing (WGS) is becoming affordable with overall costs comparable to other tests currently in use to perform the diagnosis of drug-resistant tuberculosis (TB) and cluster analysis. The WGS approach allows an "all-in-one" approach providing results on expected sensitivity of the strains, genetic background, epidemiological data, and indication of risk of laboratory cross-contamination. METHODS: Although ideal, WGS from the direct diagnostic specimen is not yet standardized, and to date the two most promising approaches are WGS from early positive liquid culture and targeted sequencing from diagnostic specimens using Next-Generation Technology...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043581/common-features-of-tuberculosis-and-sarcoidosis
#14
Esmaeil Mortaz, Mohammad Reza Masjedi, Atefeh Abedini, Soheila Matroodi, Arda Kiani, Dina Soroush, Ian M Adcock
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Despite the availability of novel therapeutic approaches, TB is considered as one of the leading causes of death due to infectious diseases worldwide. Alveolar macrophages are the first line of defense against M. tuberculosis; they ingest and sequester the bacilli within granulomatous structures. Control and resolution of the infection requires activated T lymphocytes as well as Th1 cytokines. There are two forms of TB: active TB and latent TB...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043546/molecular-identification-of-mycobacterium-tuberculosis-complex-by-region-of-differentiation-typing-and-polymerase-chain-reaction-restriction-fragment-length-polymorphism-method
#15
Seydeh Zeinab Mirzaki, Nader Mosavari, Razieh Nazari, Morteza Akbarian
Tuberculosis (TB) is one of the most common zoonotic infectious diseases in the world. Identification of Mycobacterium isolates is essential for proper treatment of TB. The aim of this study was to identify Mycobacterium isolates collected from TB patients in Alborz Province, Iran, by region of differentiation (RD)-typing. Fifty samples from tuberculosis patients were cultured in pyruvate and glycerinated Lowenstein-Jensen medium. DNA was extracted from the isolates by the van Solingen method and subjected to polymerase chain reaction (PCR)-16SrRNA, PCR-IS6110, and RD-typing with primers RD1, RD4, RD9, and RD12, respectively...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043525/molecular-genetics-of-mycobacterium-tuberculosis-resistant-to-aminoglycosides-and-cyclic-peptide-testing-by-mtbdrsl-in-armenia
#16
Hasmik Margaryan, Parissa Farnia, Armen Hayrapetyan, Alvard Mirzoyan
OBJECTIVE/BACKGROUND: The GenoType MTBDRsl test rapidly detects resistance to ethambutol, fluoroquinolones, second-line aminoglycosides (amikacin [AMK] and kanamycin [KAN]), and cyclic peptides (capreomycin [CAP]) in Mycobacterium tuberculosis. According to data from Global Drug Resistance Surveillance Report (2007), Armenia is counted as a high-burden country for multidrug-resistant tuberculosis (MDR-TB). The estimated burden of MDR-TB in 2012 was 9.4 (7-12) and 43 (38-49) among retreatment TB cases...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043516/evaluation-of-genotype-mtbdrplus-assay-for-rapid-detection-of-isoniazid-and-rifampicin-resistance-in-mycobacterium-tuberculosis-clinical-isolates-from-pakistan
#17
Hasnain Javed, Nazia Jamil, Tomasz Jagielski, Zofia Bakuła, Zarfishan Tahir
BACKGROUND: GenoType MTBDRplus is a molecular assay for detection of Mycobacterium tuberculosis resistance to isoniazid (INH) and rifampicin (RMP), the two major anti-tuberculosis (TB) drugs. Identification of INH resistance is largely based on the occurrence of mutations in the katG gene, coding for the catalase-peroxidase, or in the promoter region of the inhA gene, coding for the NADH-dependent enoyl-ACP reductase. For testing the RMP resistance, mutations in the rpoB gene, coding for the RNA polymerase β subunit, particularly in the RMP resistance determining region (RRDR) of the gene are investigated...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28024984/enhancing-yields-of-low-and-single-copy-number-plasmid-dnas-from-escherichia-coli-cells
#18
Whitney N Wood, Kyle D Smith, Jennifer A Ream, L Kevin Lewis
Many plasmids used for gene cloning and heterologous protein expression in Escherichia coli cells are low copy number or single copy number plasmids. The extraction of these types of plasmids from small bacterial cell cultures produces low DNA yields. In this study, we have quantitated yields of low copy and single copy number plasmid DNAs after growth of cells in four widely used broths (SB, SOC, TB, and 2xYT) and compared results to those obtained with LB, the most common E. coli cell growth medium. TB (terrific broth) consistently generated the greatest amount of plasmid DNA, in agreement with its ability to produce higher cell titers...
December 23, 2016: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28012685/pnca-mutations-are-associated-with-slower-sputum-conversion-during-standard-treatment-of-multidrug-resistant-tuberculosis
#19
Xubin Zheng, Zhu Ning, Francis Drobniewski, Jingyong Yang, Qun Li, Zhengdong Zhang, Yi Hu
Despite the strong association between drug resistance and genetic mutations, the value of molecular diagnosis of drug resistance to guide the treatment of multidrug-resistant tuberculosis (MDR-TB) remains unclear. This is particularly relevant in resource-limited areas where it is difficult to perform drug susceptibility testing (DST). Here we investigated the association between drug susceptibility phenotypes and genotypes and treatment outcomes in patients with MDR-TB. This study enrolled 74 consecutive patients with confirmed MDR-TB between 2010 and 2011, and outcomes were followed-up over the 24-month treatment course...
November 24, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28000585/ifn-%C3%AE-promoter-polymorphisms-do-not-affect-quantiferon%C3%A2-tb-gold-in-tube-test-results-in-a-canadian-population
#20
S Kiazyk, L Larcombe, C Lopez, S Matyas, C Mesa, P Orr, J Juno, J Waruk, M Sharma, T B Ball
BACKGROUND: Several studies have shown polymorphisms within the interferon-gamma (IFN-γ) promoter influence cytokine expression. The interferon-gamma release assay (IGRA) relies on the ability to produce IFN-γ in response to tuberculosis (TB) specific antigens. This study determined the relationship between the IFN-γ +874 A/T promoter polymorphism and the performance of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in an ethnically diverse Canadian population. METHODS: A total of 190 participants were categorised into three groups based on history of and exposure to TB: active TB (n = 55), TB exposed (n = 55) and presumably TB unexposed controls (n = 80)...
December 1, 2016: International Journal of Tuberculosis and Lung Disease
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