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https://www.readbyqxmd.com/read/28636650/the-formation-of-lipid-droplets-favors-intracellular-mycobacterium-leprae-survival-in-sw-10-non-myelinating-schwann-cells
#1
Song-Hyo Jin, Sung-Kwan An, Seong-Beom Lee
Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M...
June 21, 2017: PLoS Neglected Tropical Diseases
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
#2
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
#3
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/28636488/workers-exposure-to-bioaerosols-from-three-different-types-of-composting-facilities
#4
Laetitia Bonifait, Geneviève Marchand, Marc Veillette, Hamza M'Bareche, Marie-Eve Dubuis, Carole Pépin, Yves Cloutier, Yves Bernard, Caroline Duchaine
Composting is a natural dynamic biological process used to valorise putrescible organic matter. The composting process can involve vigorous movements of waste material piles, which release high concentrations of bioaerosols into the surrounding environment. There is a lack of knowledge concerning the dispersal of airborne microorganisms emitted by composting plants (CP) as well as the potential occupational exposure of composting workers. The aim of this study was to investigate the workers exposure to bioaerosols during working activities in three different types of composting facilities (domestic, manure, carcass) using two different quantification methods (cultivation and qPCR) for bacteria and moulds concentrations...
June 21, 2017: Journal of Occupational and Environmental Hygiene
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#5
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
#6
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/28635524/serology-and-protein-electrophoresis-for-evidence-of-exposure-to-12-mink-pathogens-in-free-ranging-american-mink-neovison-vison-in-argentina
#7
Pablo Eduardo Martino, Luis Ernesto Samartino, Néstor Oscar Stanchi, Nilda Esther Radman, Eduardo Joaquín Parrado
BACKGROUND: Basic pathologic characteristics for farmed minks were previously reported worldwide. However, its status in the wild has not been studied in detail. OBJECTIVE: Serology and electrophoresis were carried out for evidence of exposure to 12 mink pathogens on two different locations. ANIMALS AND METHODS: Serology was done in 87 wild minks by reference techniques against Toxoplasma gondii, Encephalitozoon cuniculi, Neospora caninum, Brucella abortus, Mycobacterium bovis, Leptospira interrogans, canine distemper virus (CDV), canine adenovirus (CAV), canine parvovirus (CPV), rabies virus (RV), Influenza A virus (FLUAV) and Aleutian disease virus (ADV)...
December 2017: Veterinary Quarterly
https://www.readbyqxmd.com/read/28634849/characterization-of-new-recombinant-3-ketosteroid-%C3%AE-1-dehydrogenases-for-the-biotransformation-of-steroids
#8
Xiaojun Wang, Jinhui Feng, Dalong Zhang, Qiaqing Wu, Dunming Zhu, Yanhe Ma
3-Ketosteroid-Δ(1)-dehydrogenases (KstDs [EC 1.3.99.4]) catalyze the Δ(1)-dehydrogenation of steroids and are a class of important enzymes for steroid biotransformations. In this study, we cloned 12 putative KstD-encoding (kstd) genes from both fungal and Gram-positive microorganisms and attempted to overproduce the recombinant proteins in E. coli BL21(DE3). Five successful recombinant enzymes catalyzed the Δ(1)-desaturation of a variety of steroidal compounds such as 4-androstene-3,17-dione (AD), 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), hydrocortisone, cortisone, and cortexolone...
June 20, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28634712/site-directed-mutagenesis-under-the-direction-of-in-silico-protein-docking-modeling-reveals-the-active-site-residues-of-3-ketosteroid-%C3%AE-1-dehydrogenase-from-mycobacterium-neoaurum
#9
Ning Qin, Yanbing Shen, Xu Yang, Liqiu Su, Rui Tang, Wei Li, Min Wang
3-Ketosteroid-Δ(1)-dehydrogenases (KsdD) from Mycobacterium neoaurum could transform androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione. This reaction has a significant effect on the product of pharmaceutical steroid. The crystal structure and active site residues information of KsdD from Mycobacterium is not yet available, which result in the engineering of KsdD is tedious. In this study, by the way of protein modeling and site-directed mutagenesis, we find that, Y122, Y125, S138, E140 and Y541 from the FAD-binding domain and Y365 from the catalytic domain play a key role in this transformation...
July 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28634640/the-microbiome-of-eucalyptus-roots-under-different-management-conditions-and-its-potential-for-biological-nitrogen-fixation
#10
Eduardo da Siva Fonseca, Raquel Silva Peixoto, Alexandre Soares Rosado, Fabiano de Carvalho Balieiro, James M Tiedje, Caio Tavora Coelho da Costa Rachid
Eucalyptus plantations offer a cost-effective and renewable source of raw material. There is substantial interest in improving forestry production, especially through sustainable strategies such as the use of plant growth-promoting bacteria. However, little is known about Eucalyptus microbiology. In this study, the endophytic bacterial community was assessed in Eucalyptus urograndis roots using culture-dependent and culture-independent techniques with plants grown under different conditions. Three phyla accounted for approximately 95% of the community, with Actinobacteria corresponding to approximately 59%...
June 21, 2017: Microbial Ecology
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
#11
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/28634401/ohrr-of-mycobacterium-smegmatis-senses-and-responds-to-intracellular-organic-hydroperoxide-stress
#12
Omar A Garnica, Kishore Das, Subramanian Dhandayuthapani
Organic hydroperoxide reductase regulator (OhrR) in bacteria is a sensor for organic hydroperoxide stress and a transcriptional regulator for the enzyme organic hydroperoxide reductase (Ohr). In this study we investigated, using a GFP reporter system, whether Mycobacterium smegmatis OhrR has the ability to sense and respond to intracellular organic hydroperoxide stress. It was observed that M. smegmatis strains bearing the pohr-gfpuv fusion construct were able to express GFP only in the absence of an intact ohrR gene, but not in its presence...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634299/biosynthesis-of-isonitrile-lipopeptides-by-conserved-nonribosomal-peptide-synthetase-gene-clusters-in-actinobacteria
#13
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/28633708/once-daily-dosing-of-amikacin-for-treatment-of-mycobacterium-abscessus-lung-disease
#14
H Lee, Y M Sohn, J Y Ko, S-Y Lee, B W Jhun, H Y Park, K Jeon, D H Kim, S-Y Kim, J E Choi, I J Moon, S J Shin, H J Park, W-J Koh
SETTING: Tertiary referral centre, Samsung Medical Center, South Korea. OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. DESIGN: A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 μg/ml was achieved in 31...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633705/household-food-insecurity-is-associated-with-low-interferon-gamma-levels-in-pregnant-indian-women
#15
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
#16
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
#17
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/28633333/anti-natural-octyl-disaccharide-leprosy-idri-diagnostic-ndo-lid-antibodies-as-indicators-of-leprosy-reactions-and-neuritis
#18
Héctor Serrano-Coll, Mónica Muñoz, Juan Camilo Beltrán, Malcolm S Duthie, Nora Cardona-Castro
Background: Leprosy is a complex infectious and neurological disease caused by Mycobacterium leprae. Nerve damage is related to immunological hypersensitivity responses known as leprosy reactions (LRs). Diagnostic tools to predict LRs are not available. We hypothesized that natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) would be helpful as an indicator of LRs and neuritis. Methods: To assess the utility of NDO-LID in indicating reactions, ELISA were used to detect specific antibodies in serum samples from 80 Colombian leprosy patients (40 with and 40 without history of LRs)...
March 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28633259/mycobacterium-chimaera-infection-after-cardiac-surgery-first-canadian-outbreak
#19
Raphael Hamad, Pierre-Emmanuel Noly, Louis P Perrault, Michel Pellerin, Philippe Demers
Recently reported in Europe and United States, disseminated Mycobacterium chimaera infection is a novel clinical entity linked to point contamination of Stockert 3T heater-cooler units used for cardiopulmonary bypass. We present here the first two cases in Canada. Both patients presented with nonspecific extracardiac symptoms 1 year after undergoing minimally invasive mitral surgical repair. Before the right diagnosis was established, the patients were initially treated with prednisone for suspected sarcoidosis...
July 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#20
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
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