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(Mycobacterium AND Tuberculosis)

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https://www.readbyqxmd.com/read/28636635/microrna-144-3p-inhibits-autophagy-activation-and-enhances-bacillus-calmette-gu%C3%A3-rin-infection-by-targeting-atg4a-in-raw264-7-macrophage-cells
#1
Le Guo, Linlin Zhou, Qian Gao, Aijun Zhang, Jun Wei, Dantong Hong, Yuankui Chu, Xiangguo Duan, Ying Zhang, Guangxian Xu
MicroRNAs (miRNAs) are small noncoding nucleotides that play major roles in the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M. tuberculosis). Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection is largely unknown. In the present study, we demonstrate that Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection of macrophages leads to increased expression of miR-144-3p, which targets autophagy-related gene 4a (ATG4a), to inhibit autophagy activation and antimicrobial responses to BCG...
2017: PloS One
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#2
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#3
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635627/molecular-quantum-similarity-chemical-reactivity-and-database-screening-of-3d-pharmacophores-of-the-protein-kinases-a-b-and-g-from-mycobacterium-tuberculosis
#4
Alejandro Morales-Bayuelo
Mycobacterium tuberculosis remains one of the world's most devastating pathogens. For this reason, we developed a study involving 3D pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases A, B, and G. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these compounds, with anti-tuberculosis activity...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#5
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634299/biosynthesis-of-isonitrile-lipopeptides-by-conserved-nonribosomal-peptide-synthetase-gene-clusters-in-actinobacteria
#6
Nicholas C Harris, Michio Sato, Nicolaus A Herman, Frederick Twigg, Wenlong Cai, Joyce Liu, Xuejun Zhu, Jordan Downey, Ryan Khalaf, Joelle Martin, Hiroyuki Koshino, Wenjun Zhang
A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28633705/household-food-insecurity-is-associated-with-low-interferon-gamma-levels-in-pregnant-indian-women
#7
A Vaidya, R Bhosale, P Sambarey, N Suryavanshi, S Young, V Mave, S Kanade, V Kulkarni, P Deshpande, U Balasubramanian, J Elf, N Gupte, A Gupta, J S Mathad
SETTING: Over 20% of tuberculosis (TB) cases during pregnancy occur in India. OBJECTIVE: To determine the association between household food insecurity and interferon-gamma (IFN-γ) levels in pregnancy. DESIGN: Pregnant women in India were administered the Household Food Insecurity Access Scale (HFIAS) questionnaire and underwent an IFN-γ release assay. Logistic regression was used to identify factors associated with food insecurity. RESULTS: Of 538 women, 60 (11%) had household food insecurity, 47 (78%) of which were moderate or severe food insecure...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633695/how-should-discordance-between-molecular-and-growth-based-assays-for-rifampicin-resistance-be-investigated
#8
S Hofmann-Thiel, H Hoffmann, D Hillemann, L Rigouts, A Van Deun, K Kranzer
Molecular tests to detect the presence of Mycobacterium tuberculosis and genetic polymorphisms in the rpoB gene conferring resistance to rifampicin (RMP) have become integral parts of tuberculosis diagnostics worldwide. These assays are often performed sequentially or in parallel to phenotypic drug susceptibility testing. Discordances between molecular and phenotypic tests invariably occur. Root causes range from pre-, post- and analytic errors to co-existence of non-tuberculous mycobacteria, silent mutations, mutations outside the 81 base-pair RMP resistance-determining region, non-canonical mutations conferring increased minimal inhibitory concentrations below the critical concentration in some phenotypic drug susceptibility tests, and heteroresistance...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633546/identification-of-specific-antibodies-against-the-ag85c-mpt51-hspx-fusion-protein-cmx-for-serological-screening-of-tuberculosis-in-endemic-area
#9
Adrielle Zagmignan, Adeliane Castro da Costa, José Lima Viana, Lídio Gonçalves Lima Neto, Cristina de Andrade Monteiro, Ariosvaldo Guimarães Gaioso Neto, Ana Paula Junqueira Kipnis, Eduardo M de Sousa
OBJECTIVES: Development of new tools for rapid and accurate diagnosis of tuberculosis (TB) is considered a strategy for controlling the disease. The recombinant CMX fusion protein is composed of immunodominant epitopes of the Ag85C (Rv0129c), MPT51 (Rv3803c) and the entire HspX (Rv2031c) proteins from Mycobacterium tuberculosis H37Rv (Mtb). The aim of this study was to evaluate the applicability of a test using the CMX protein in individuals suspected of TB. METHODS: Indirect ELISA was used to measure serum anti-CMX IgM and IgG in individuals with pulmonary TB...
June 21, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#10
Stefania Spanò, Jorge E Galán
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632406/tailored-pharmacophore-model-to-enhance-virtual-screening-and-drug-discovery-a-case-study-on-the-identification-of-potential-inhibitors-against-drug-resistant-mycobacterium-tuberculosis-3r-hydroxyacyl-acp-dehydratases
#11
Kgothatso E Machaba, Ndumiso N Mhlongo, Yussif M Dokurugu, Mahmoud Es Soliman
AIM: Virtual screening (VS) is powerful tool in discovering molecular inhibitors that are most likely to bind to drug targets of interest. Herein, we introduce a novel VS approach, so-called 'tailored-pharmacophore', in order to explore inhibitors that overcome drug resistance. Methodology & results: The emergence and spread of drug resistance strains of tuberculosis is one of the most critical issues in healthcare. A tailored-pharmacophore approach was found promising to identify in silico predicted hit with better binding affinities in case of the resistance mutations in MtbHadAB as compared with thiacetazone, a prodrug used in the clinical treatment of tuberculosis...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28631943/evaluation-of-the-genotype-mtbdrsl-test-for-detection-of-second-line-drug-resistance-in-drug-resistant-mycobacterium-tuberculosis-strains-in-myanmar
#12
Wint Wint Nyunt, Si Thu Aung, Gregory M Cook, Htin Lin Aung
No abstract text is available yet for this article.
June 20, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28631644/evaluation-of-a-new-rapid-kit-bd-mgit-tbc-identification-test-for-confirmation-of-mycobacterium-tuberculosis-complex
#13
Gandhi Kandhakumari, Selvaraj Stephen
At present, three rapid kits are available globally for the confirmation of Mycobacterium tuberculosis complex (MTBC) in cultures by MPT64 antigen (MPT64 Ag) detection. These include Capilia TB, SD Bioline, and BD MGIT TBc Identification (TBcID). The third kit is yet to be validated in India. We have tested this kit and compared with SD Bioline using conventional tests as gold standard. Seventy-one MTBC (70 M. tuberculosis and one Mycobacterium bovis) and four nontuberculous mycobacteria (NTM) were isolated from 649 clinical specimens in MGIT 960 and/or Lowenstein-Jensen slants (LJ)...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28631643/multidrug-resistant-tuberculosis-detection-and-characterization-of-mutations-in-mycobacterium-tuberculosis-by-genotype-mtbdrplus
#14
Rajneesh Tripathi, Shampa Anupurba
Detection of drug resistance in Mycobacterium tuberculosis by conventional phenotypic drug susceptibility testing methods requires several weeks. Therefore, molecular diagnostic tests for rapid detection of multidrug resistance tuberculosis (MDR-TB) are urgently needed. Early diagnosis helps in initiating optimal treatment which would not only enable cure of an individual patient but also will curb the transmission of drug resistance in the community. Line probe assay (LPA) has shown great promises in the diagnosis of MDR-TB...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28630430/a-multinational-analysis-of-mutations-and-heterogeneity-in-pzase-rpsa-and-pand-associated-with-pyrazinamide-resistance-in-m-xdr-mycobacterium-tuberculosis
#15
S M Ramirez-Busby, T C Rodwell, L Fink, D Catanzaro, R L Jackson, M Pettigrove, A Catanzaro, F Valafar
Pyrazinamide (PZA) is an important first-line drug in all existing and new tuberculosis (TB) treatment regimens. PZA-resistance in M. tuberculosis is increasing, especially among M/XDR cases. Noted issues with PZA Drug Susceptibility Testing (DST) have driven the search for alternative tests. This study provides a comprehensive assessment of PZA molecular diagnostics in M/XDR TB cases. A set of 296, mostly XDR, clinical M. tuberculosis isolates from four countries were subjected to DST for eight drugs, confirmatory Wayne's assay, and whole-genome sequencing...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630205/the-impact-of-gyrb-and-eis-mutations-in-improving-second-line-drug-resistance-detection-among-mycobacterium-tuberculosis-isolates-from-georgia
#16
N Bablishvili, N Tukvadze, E Shashkina, B Mathema, N R Gandhi, H M Blumberg, R R Kempker
SETTING: The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB).OBJECTIVE: To evaluate whether the detection of mutations in gyrB and eis genes increased the sensitivity of detecting phenotypic resistance to ofloxacin and kanamycin or capreomycin as compared to use of the first generation MTBDRsl assay alone which evaluates for mutations in gyrA and rrs genes.DESIGN: A retrospective study of storedMycobacterium tuberculosis isolates. All isolates underwent DNA sequencing of resistance determining regions...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630193/pyrazinamide-susceptibility-and-pnca-mutation-profile-of-mycobacterium-tuberculosis-among-multi-drug-resistant-tuberculosis-patients-in-bangladesh
#17
Arfatur Rahman, Sara Sabrina Ferdous, Shahriar Ahmed, S M Mazidur Rahman, Mohammad Khaja Mafij Uddin, Suporn Pholwat, Jean Gratz, Eric Houpt, Sayera Banu
Pyrazinamide (PZA) is a front line anti-tuberculosis (anti-TB) drug used in both first and second line treatment regimen. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed leading to the scarcity of data. Bangladesh is both a high TB and multi-drug resistant (MDR-TB) burden country but to our knowledge the published data on PZA susceptibility is limited, especially among MDR-TB patients. We aimed to analyze the PZA susceptibility pattern of Mycobacterium tuberculosis (MTB) isolates from MDR-TB patients and to correlate pncA mutation with PZA resistance in Bangladesh...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#18
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28629614/molecular-detection-methods-of-resistance-to-antituberculosis-drugs-in-mycobacterium-tuberculosis
#19
F Brossier, W Sougakoff
OBJECTIVE: Molecular methods predict drug resistance several weeks before phenotypic methods and enable rapid implementation of appropriate therapeutic treatment. We aimed to detail the most representative molecular tools used in routine practice for the rapid detection of resistance to antituberculosis drugs among Mycobacterium tuberculosis strains. MATERIALS AND METHODS: The molecular diagnosis of resistance to antituberculosis drugs in clinical samples or from in vitro cultures is based on the detection of the most common mutations in the genes involved in the development of resistance in M...
June 16, 2017: Médecine et Maladies Infectieuses
https://www.readbyqxmd.com/read/28629354/acetone-leaf-extracts-of-some-south-african-trees-with-high-activity-against-escherichia-coli-also-have-good-antimycobacterial-activity-and-selectivity-index
#20
Ishaku L Elisha, Francien S Botha, Balungile Madikizela, Lyndy J McGaw, Jacobus N Eloff
BACKGROUND: Tuberculosis is a world-wide problem affecting humans and animals. There is increasing development of resistance of the pathogens to current antimycobacterial agents. Many authors have investigated activities of extracts and isolated compounds from plants. The traditional uses of plants have frequently been the criterion to select plants investigated. In this contribution, we investigate whether plant extracts with very good activity against Escherichia coli may also be active against mycobacteria...
June 19, 2017: BMC Complementary and Alternative Medicine
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