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https://www.readbyqxmd.com/read/28436453/functional-thermodynamics-structural-and-biological-studies-of-in-silico-identified-inhibitors-of-mycobacterium-tuberculosis-enoyl-acp-coa-reductase-enzyme
#1
Leonardo K B Martinelli, Mariane Rotta, Anne D Villela, Valnês S Rodrigues-Junior, Bruno L Abbadi, Rogério V Trindade, Guilherme O Petersen, Giuliano M Danesi, Laura R Nery, Ivani Pauli, Maria M Campos, Carla D Bonan, Osmar Norberto de Souza, Luiz A Basso, Diogenes S Santos
Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436419/nontuberculous-mycobacteria-in-gastrostomy-fed-patients-with-cystic-fibrosis
#2
H Al-Momani, A Perry, R Jones, S Bourke, S Doe, J Perry, A Anderson, T Forrest, I Forrest, M Griffin, M Brodlie, J Pearson, C Ward
Multi-drug resistant Mycobacterium abscessus complex (MABSC) is a form of Nontuberculous mycobacteria (NTM) of special, international concern in Cystic Fibrosis (CF). We hypothesised that gastric juice and percutaneous endoscopic gastrostomy (PEG) feeding devices might yield MABSC isolates. Gastric juice and sputa from sixteen adult PEG fed CF patients and five replaced PEG tubes were studied. Bacterial and fungal isolates were cultured. Mycobacterium were identified by rpoB, sodA and hsp65 gene sequencing and strain typed using variable number tandem repeat...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28434972/one-bacillus-to-rule-them-all-investigating-broad-range-host-adaptation-in-mycobacterium-bovis
#3
REVIEW
Adrian R Allen
Recent advances are permitting researchers to undertake largescale comparative genomics studies within and between bacterial species to determine the types of genetic change that underpin the phenotypic spectrum that runs from strict host adaptation to generalist. Within the Mycobacterium tuberculosis complex (MTBC) of bacilli, there is much heterogeneity in host specificity. Globally, Mycobacterium bovis exhibits a broad host range encompassing domesticated bovine and wildlife animals unlike the human adapted specialist M...
April 20, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28433210/non-tuberculous-mycobacteria-an-emerging-threat
#4
Susana Martínez González, Arantxa Cano Cortés, Luis Alfonso Sota Yoldi, José María García García, Luz María Alba Álvarez, Juan José Palacios Gutiérrez
INTRODUCTION AND OBJECTIVE: Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. METHODOLOGY: Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines...
April 19, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/28429679/mycobacterium-avium-complex-disease
#5
Charles L Daley
Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28429162/involvement-of-methylated-hbha-expressed-from-mycobacterium-smegmatis-in-an-ifn-%C3%AE-release-assay-to-aid-discrimination-between-latent-infection-and-active-tuberculosis-in-bcg-vaccinated-populations
#6
H-L Wen, C-L Li, G Li, Y-H Lu, H-C Li, T Li, H-M Zhao, K Wu, D B Lowrie, J-X Lv, S-H Lu, X-Y Fan
IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis (M. tb) infection. However, IGRAs with these antigens cannot discriminate between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin (HBHA) induces relatively high IFN-γ responses in LTBI individuals and low responses in ATB patients, but purification of the native methylated HBHA from cultures of M. tb for immunological tests is complex and time-consuming...
April 20, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#7
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28427555/impact-of-cavity-and-infiltration-on-pulmonary-function-and-health-related-quality-of-life-in-pulmonary-mycobacterium-avium-complex-disease-a-3-dimensional-computed-tomographic-analysis
#8
Takanori Asakura, Yoshitake Yamada, Ho Namkoong, Shoji Suzuki, Yuki Niijima, Hirofumi Kamata, Yohei Funatsu, Kazuma Yagi, Satoshi Okamori, Hiroaki Sugiura, Makoto Ishii, Masahiro Jinzaki, Tomoko Betsuyaku, Naoki Hasegawa
BACKGROUND AND OBJECTIVES: Pulmonary Mycobacterium avium complex (pMAC) disease manifests as various types of lesions, such as infiltrates, nodules, cavities, and bronchiectasis. However, the important determinants for clinical parameters in lung involvement are poorly understood. The objective of this study was to obtain quantitative parameters by 3-dimensional CT, and investigate the relationship between these parameters and the pulmonary function tests (PFTs) and health-related quality of life...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28423094/complications-of-chronic-necrotizing-pulmonary-aspergillosis-review-of-published-case-reports
#9
Aleksandra Barac, Tatjana Adzic Vukicevic, Aleksandra Dudvarski Ilic, Salvatore Rubino, Vladimir Zugic, Goran Stevanovic
Chronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons with underlying pulmonary disease. These conditions are associated with high morbidity and mortality and often require long-term antifungal treatment. The long-term prognosis for patients with CNPA and the potential complications of CNPA have not been well documented. The aim of this study was to review published papers that report cases of CNPA complications and to highlight risk factors for development of CNPA...
April 13, 2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/28422568/cgas-sting-tbk1-irf3-7-induced-interferon-%C3%AE-contributes-to-the-clearing-of-non-tuberculous-mycobacterial-infection-in-mice
#10
Nanthapon Ruangkiattikul, Andreas Nerlich, Ketema Abdissa, Stefan Lienenklaus, Abdulhadi Suwandi, Nina Janze, Kristin Laarmann, Julia Spanier, Ulrich Kalinke, Siegfried Weiss, Ralph Goethe
Type I interferons (IFN-I), such as IFN-α and IFN-β are important messengers in the host response against bacterial infections. Knowledge about the role of IFN-I in infections by nontuberculous mycobacteria (NTM) is limited. Here we show that macrophages infected with pathogens of the Mycobacterium avium complex produced significantly lower amounts of IFN-β than macrophages infected with the opportunistic pathogen M. smegmatis. To dissect the molecular mechanisms of this phenomenon, we focussed on the obligate pathogen Mycobacterium avium ssp...
April 19, 2017: Virulence
https://www.readbyqxmd.com/read/28418290/invasive-nontuberculous-mycobacterial-infections-among-cardiothoracic-surgical-patients-exposed-to-heater-cooler-devices-1
#11
Meghan M Lyman, Cheri Grigg, Cara Bicking Kinsey, M Shannon Keckler, Heather Moulton-Meissner, Emily Cooper, Minn M Soe, Judith Noble-Wang, Allison Longenberger, Shane R Walker, Jeffrey R Miller, Joseph F Perz, Kiran M Perkins
Invasive nontuberculous mycobacteria (NTM) infections may result from a previously unrecognized source of transmission, heater-cooler devices (HCDs) used during cardiac surgery. In July 2015, the Pennsylvania Department of Health notified the Centers for Disease Control and Prevention (CDC) about a cluster of NTM infections among cardiothoracic surgical patients at 1 hospital. We conducted a case-control study to identify exposures causing infection, examining 11 case-patients and 48 control-patients. Eight (73%) case-patients had a clinical specimen identified as Mycobacterium avium complex (MAC)...
May 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28416386/structural-analysis-of-the-interaction-between-spiroisoxazoline-smart-420-and-the-mycobacterium-tuberculosis-repressor-ethr2
#12
Alexandre Wohlkönig, Han Remaut, Martin Moune, Abdalkarim Tanina, Franck Meyer, Matthieu Desroses, Jan Steyaert, Nicolas Willand, Alain R Baulard, René Wintjens
Inhibition of transcriptional regulators of bacterial pathogens with the aim of reprogramming their metabolism to modify their antibiotic susceptibility constitutes a promising therapeutic strategy. One example is the bio-activation of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by inhibiting the transcriptional repressor EthR. Recently, we discovered that inhibition of a second transcriptional repressor, EthR2, leads to the awakening of a new ethionamide bio-activation pathway...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28416214/corrigendum-to-nothing-to-s-cough-at-pulmonary-mycobacterium-avium-complex-infection-am-j-med-2017-130-2-153-156
#13
Michael A Santos, Hardikkumar Patel, Adam Albert
No abstract text is available yet for this article.
April 14, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28414774/mycobacterium-marinum-antagonistically-induces-an-autophagic-response-while-repressing-the-autophagic-flux-in-a-torc1-and-esx-1-dependent-manner
#14
Elena Cardenal-Muñoz, Sonia Arafah, Ana Teresa López-Jiménez, Sébastien Kicka, Alexandra Falaise, Frauke Bach, Olivier Schaad, Jason S King, Monica Hagedorn, Thierry Soldati
Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium...
April 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28413773/a-m-%C3%A2-avium-complex-spondylodiscitis-in-a-middle-aged-woman-with-diabetes
#15
Irini Gerogianni, Stylianos Boutlas, Theophilos Karachalios, Eythymia Petinaki, Marianna Vlychou, K I Gourgoulianis
Spondylodiscitis, the inflammation of the vertebral bodies and the intervertebral disk space, is the reason for low back pain in a minority of cases. This is caused by various pathogens. Mycobacterium tuberculosis is responsible for 17-39% of all the cases of spondylodiscitis. On the contrast, spondylodiscitis from non tuberculous mycobacteria is extremely rare in literature. We describe a 68 -year old diabetic woman which is the first case of bone marrow involvement by M. intracellulare (member of M avium complex)with spondylodiscitis...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28410694/pyridines-multidrug-resistant-tuberculosis-mdr-tb-inhibitors
#16
REVIEW
Kavita S Chaudhari, Harun M Patel, Sanjay J Surana
Mycobacterium tuberculosis (MTB) infection has become an increasing health threat due to the worldwide emergence of multidrug-resistant MTB (MDR-MTB) strain. Isoniazid (pyridine) resistance problem is a complex process and is associated with mutations in several genes. However, the emergence of isoniazid (INH) resistant M. tuberculosis strains dictates the necessity for redesigning this old drug in order to create analogs effective against INH-resistant strains by using rational approach. In light of these findings, the present review discusses the synthesis, structural optimization, and modification in pyridine structure to combat the problem of multidrug-resistant tuberculosis...
April 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28407432/diagnosis-of-biofilm-infections-in-cystic-fibrosis-patients
#17
REVIEW
Niels Høiby, Thomas Bjarnsholt, Claus Moser, Peter Østrup Jensen, Mette Kolpen, Tavs Qvist, Kasper Aanaes, Tanja Pressler, Marianne Skov, Oana Ciofu
Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is dominated by alginate and the pathogenesis of tissue damage is immune complex-mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where aggregates of the bacteria are found surrounded by the abundant alginate matrix...
April 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28404571/early-detection-of-circulating-antigen-and-igm-associated-immune-complexes-during-experimental-mycobacterium-bovis-infection-in-cattle
#18
Konstantin P Lyashchenko, Rena Greenwald, Alina Sikar-Gang, Archana A Sridhara, Ashley Johnathan, Paul Lambotte, Javan Esfandiari, Mayara F Maggioli, Tyler C Thacker, Mitchell V Palmer, W Ray Waters
The presence of circulating antigen in cattle experimentally infected with Mycobacterium bovis was demonstrated using dual-path platform (DPP) technology. The antigen-capture immunoassays employed rabbit polyclonal antibody recognizing predominantly M. tuberculosis complex-specific epitopes and were able to detect soluble substances and whole cells of mycobacteria. The antigen found in serum appeared to be mostly bound to IgM, but not to IgG, within the immune complexes formed at early stages of M. bovis infection...
April 12, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28401156/computational-identification-and-characterization-of-a-promiscuous-t-cell-epitope-on-the-extracellular-protein-85b-of-mycobacterium-spp-for-peptide-based-subunit-vaccine-design
#19
Md Saddam Hossain, Abul Kalam Azad, Parveen Afroz Chowdhury, Mamoru Wakayama
Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins of Mycobacterium spp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28400527/targeting-energy-metabolism-in-mycobacterium-tuberculosis-a-new-paradigm-in-antimycobacterial-drug-discovery
#20
REVIEW
Dirk Bald, Cristina Villellas, Ping Lu, Anil Koul
Drug-resistant mycobacterial infections are a serious global health challenge, leading to high mortality and socioeconomic burdens in developing countries worldwide. New innovative approaches, from identification of new targets to discovery of novel chemical scaffolds, are urgently needed. Recently, energy metabolism in mycobacteria, in particular the oxidative phosphorylation pathway, has emerged as an object of intense microbiological investigation and as a novel target pathway in drug discovery. New classes of antibacterials interfering with elements of the oxidative phosphorylation pathway are highly active in combating dormant or latent mycobacterial infections, with a promise of shortening tuberculosis chemotherapy...
April 11, 2017: MBio
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