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Cell cycle tuberculosis

Valentina Guerrini, Selvakumar Subbian, Pierre Santucci, Stéphane Canaan, Maria Laura Gennaro, Gianni Pozzi
Isolates of the human pathogen Mycobacterium tuberculosis recovered from clinical samples exhibit genetic heterogeneity. Such variation may result from the stressful environment encountered by the pathogen inside the macrophage, which is the host cell tubercle bacilli parasitize. To study the evolution of the M. tuberculosis genome during growth inside macrophages, we developed a model of intracellular culture in which bacteria were serially passaged in macrophage-like THP-1 cells for about 80 bacterial generations...
2016: PloS One
Arbind Kumar, Pratibha Maan, Gurpreet Singh, Jagdeep Kaur
BACKGROUND: Death toll due to tuberculosis is still rising day by day. Whole genome sequence of Mycobacterium tuberculosis has provided a platform to conduct research in order to identify the probable drug target. OBJECTIVES: Out of 4000 gene products of M. tuberculosis, approximately 40% of proteins are annotated as hypothetical. Identifying and characterizing these proteins could provide a new prescriptive for developing new TB drugs. Rv1288, a protein of M. tuberculosis H37Rv has been annotated as a hypothetical protein in database...
November 24, 2016: Current Computer-aided Drug Design
Xavier A Kayigire, Sven O Friedrich, Miriam N Karinja, Lize van der Merwe, Neil A Martinson, Andreas H Diacon
Propidium monoazide (PMA) penetrates non-viable cells with compromised membranes. PMA has been proposed to improve the specificity of Xpert MTB/RIF (Xpert) for the detection of viable Mycobacterium tuberculosis. This study assessed the effect of PMA on Xpert cycle thresholds (CT) of M. tuberculosis made non-viable under antibiotic pressure. In vitro, we measured the difference between CT with and without PMA (ΔCT) in liquid cultures treated with one of six anti-tuberculosis drugs (isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, moxifloxacin) and found significant ΔCT only with isoniazid and ethambutol for pan-susceptible M...
December 2016: Tuberculosis
Pierre Santucci, Feriel Bouzid, Nabil Smichi, Isabelle Poncin, Laurent Kremer, Chantal De Chastellier, Michel Drancourt, Stéphane Canaan
Despite a slight decline since 2014, tuberculosis (TB) remains the major deadly infectious disease worldwide with about 1.5 million deaths each year and with about one-third of the population being latently infected with Mycobacterium tuberculosis, the etiologic agent of TB. During primo-infection, the recruitment of immune cells leads to the formation of highly organized granulomas. Among the different cells, one outstanding subpopulation is the foamy macrophage (FM), characterized by the abundance of triacylglycerol-rich lipid bodies (LB)...
2016: Frontiers in Cellular and Infection Microbiology
Ekta Lachmandas, Macarena Beigier-Bompadre, Shih-Chin Cheng, Vinod Kumar, Arjan van Laarhoven, Xinhui Wang, Anne Ammerdorffer, Lily Boutens, Dirk de Jong, Thirumala-Devi Kanneganti, Mark S Gresnigt, Tom H M Ottenhoff, Leo A B Joosten, Rinke Stienstra, Cisca Wijmenga, Stefan H E Kaufmann, Reinout van Crevel, Mihai G Netea
Cells in homeostasis metabolize glucose mainly through the tricarboxylic acid cycle and oxidative phosphorylation, while activated cells switch their basal metabolism to aerobic glycolysis. In this study, we examined whether metabolic reprogramming toward aerobic glycolysis is important for the host response to Mycobacterium tuberculosis (Mtb). Through transcriptional and metabolite analysis we show that Mtb induces a switch in host cellular metabolism toward aerobic glycolysis in human peripheral blood mononuclear cells (PBMCs)...
November 2016: European Journal of Immunology
Sonia Menon, Rodolfo Rossi, Leon Nshimyumukiza, Aibibula Wusiman, Natasha Zdraveska, Manal Shams Eldin
BACKGROUND: On a global scale, nearly two billion persons are infected with Mycobacterium tuberculosis. From this vast reservoir of latent tuberculosis (TB) infection, a substantial number will develop active TB during their lifetime, with some being able to transmit TB or Multi-drug- resistant (MDR) TB to others. There is clinical evidence pointing to a higher prevalence of infectious diseases including TB among individuals with Diabetes Mellitus (DM). Furthermore, ageing and diabetes mellitus may further aggravate protein-energy malnutrition (PEM), which in turn impairs T-lymphocyte mediated immunologic defenses, thereby increasing the risk of developing active TB and compromising TB treatment...
2016: BMC Infectious Diseases
Shainaba A Saadhali, Sameer Hassan, Luke Elizabeth Hanna, Uma Devi Ranganathan, Vanaja Kumar
Mycobacteriophages produce lysins that break down the host cell wall at the end of lytic cycle to release their progenies. The ability to lyse mycobacterial cells makes the lysins significant. Mycobacteriophage Che12 is the first reported temperate phage capable of infecting and lysogenising Mycobacterium tuberculosis. Gp11 of Che12 was found to have Chitinase domain that serves as endolysin (lysin A) for Che12. Structure of gp11 was modeled and evaluated using Ramachandran plot in which 98 % of the residues are in the favored and allowed regions...
August 2016: Journal of Molecular Modeling
Adam Heikal, Kiel Hards, Chen-Yi Cheung, Ayana Menorca, Mattie S M Timmer, Bridget L Stocker, Gregory M Cook
OBJECTIVES: Quinolinequinones (QQ) have been shown to inhibit the growth of mycobacterial species, but their mode(s) of action and molecular target(s) remain unknown. To facilitate further development of QQ as antimycobacterial drugs, we investigated the molecular mechanism and target of QQ in mycobacteria. METHODS: Cell viability of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin was determined in the presence of QQ8c, a representative QQ compound, and isoniazid, a frontline antitubercular drug...
October 2016: Journal of Antimicrobial Chemotherapy
Yuki Teramura, Kazuaki Kameda, Junya Kanda, Ayumi Gomyo, Jin Hayakawa, Yu Akahoshi, Yusuke Komiya, Naonori Harada, Tomotaka Ugai, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Hidenori Wada, Kiriko Terasako-Saito, Shun-Ichi Kimura, Misato Kikuchi, Hideki Nakasone, Shinichi Kako, Yoshinobu Kanda
The patient was a 62-year-old woman with CD5(+) diffuse large B-cell lymphoma. Treatment with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) was started. On the eleventh day of the third cycle, headache and low grade fever developed. Her consciousness gradually deteriorated. Seven days after symptom onset, she was brought to the emergency department of our hospital. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 25/μl, and a protein level of 188 mg/dl...
May 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Wanisa Salaemae, Grant W Booker, Steven W Polyak
Biotin is an essential cofactor for enzymes present in key metabolic pathways such as fatty acid biosynthesis, replenishment of the tricarboxylic acid cycle, and amino acid metabolism. Biotin is synthesized de novo in microorganisms, plants, and fungi, but this metabolic activity is absent in mammals, making biotin biosynthesis an attractive target for antibiotic discovery. In particular, biotin biosynthesis plays important metabolic roles as the sole source of biotin in all stages of the Mycobacterium tuberculosis life cycle due to the lack of a transporter for scavenging exogenous biotin...
April 2016: Microbiology Spectrum
W Langsteger, A Rezaee, W Loidl, H S Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M Beheshti, L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W Langsteger, A Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M Hartenbach, T Beyer, K Herrmann, J Czernin, I Rausch, P Rust, M D DiFranco, M Lassen, A Stadlbauer, M E Mayerhöfer, M Hartenbach, M Hacker, T Beyer, K Binzel, R Magnussen, W Wei, M U Knopp, D C Flanigan, C Kaeding, M V Knopp, A Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A Haug, Wencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas Kluge, C L Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, M V Knopp, M Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, R P Baum, B Knäusl, D Georg, M Bauer, B Wulkersdorfer, W Wadsak, C Philippe, H Haslacher, M Zeitlinger, O Langer, M Bauer, M Feldmann, R Karch, W Wadsak, M Zeitlinger, M J Koepp, M-C Asselin, E Pataraia, O Langer, M Zeilinger, C Philippe, M Dumanic, F Pichler, J Pilz, M Hacker, W Wadsak, M Mitterhauser, L Nics, B Steiner, M Hacker, M Mitterhauser, W Wadsak, A Traxl, Thomas Wanek, Kushtrim Kryeziu, Severin Mairinger, Johann Stanek, Walter Berger, Claudia Kuntner, Oliver Langer, S Mairinger, T Wanek, A Traxl, M Krohn, J Stanek, T Filip, M Sauberer, C Kuntner, J Pahnke, O Langer, D Svatunek, C Denk, M Wilkovitsch, T Wanek, T Filip, C Kuntner-Hannes, J Fröhlich, H Mikula, C Denk, D Svatunek, T Wanek, S Mairinger, J Stanek, T Filip, J Fröhlich, H Mikula, C Kuntner-Hannes, T Balber, J Singer, J Fazekas, C Rami-Mark, N Berroterán-Infante, E Jensen-Jarolim, W Wadsak, M Hacker, H Viernstein, M Mitterhauser, C Denk, D Svatunek, B Sohr, H Mikula, J Fröhlich, T Wanek, C Kuntner-Hannes, T Filip, S Pfaff, C Philippe, M Mitterhauser, M Hartenbach, M Hacker, W Wadsak, T Wanek, E Halilbasic, M Visentin, S Mairinger, B Stieger, C Kuntner, M Trauner, O Langer, P Lam, M Aistleitner, R Eichinger, C Artner, H Eidherr, C Vraka, A Haug, M Mitterhauser, L Nics, M Hartenbach, M Hacker, W Wadsak, H Kvaternik, R Müller, D Hausberger, C Zink, R M Aigner, U Cossío, M Asensio, A Montes, S Akhtar, Y Te Welscher, R van Nostrum, V Gómez-Vallejo, J Llop, F VandeVyver, T Barclay, N Lippens, M Troch, L Hehenwarter, B Egger, J Holzmannhofer, M Rodrigues-Radischat, C Pirich, N Pötsch, I Rausch, D Wilhelm, M Weber, J Furtner, G Karanikas, A Wöhrer, M Mitterhauser, M Hacker, T Traub-Weidinger, T Cassou-Mounat, S Balogova, V Nataf, M Calzada, V Huchet, K Kerrou, J-Y Devaux, M Mohty, L Garderet, J-N Talbot, S Stanzel, G Pregartner, T Schwarz, V Bjelic-Radisic, B Liegl-Atzwanger, R Aigner, S Stanzel, F Quehenberger, R M Aigner, A Koljević Marković, Milica Janković, V Miler Jerković, M Paskaš, G Pupić, R Džodić, D Popović, M C Fornito, D Familiari, P Koranda, H Polzerová, I Metelková, L Henzlová, R Formánek, E Buriánková, M Kamínek, W H Thomson, C Lewis, W H Thomson, J O'Brien, G James, A Notghi, H Huber, I Stelzmüller, R Wunn, M Mandl, F Fellner, B Lamprecht, M Gabriel, M C Fornito, G Leonardi, W H Thomson, J O'Brien, G James, J Hudzietzová, J Sabol, M Fülöp
A1 68Ga-PSMA PET/CT in staging and restaging of Prostate Cancer Patients: comparative study with 18F-Choline PET/CTW Langsteger, A Rezaee, W Loidl, HS Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M BeheshtiA2 F18 Choline PET - CT: an accurate diagnostic tool for the detection of parathyroid adenoma?L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W LangstegerA3 [18F]Fluoro-DOPA-PET/CT in the primary diagnosis of medullary thyroid carcinomaA Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M HartenbachA4 Variations of clinical PET/MR operations: An international survey on the clinical utilization of PET/MRIT Beyer, K Herrmann, J CzerninA5 Standard Dixon-based attenuation correction in combined PET/MRI: Reproducibility and the possibility of Lean body mass estimationI Rausch, P Rust, MD DiFranco, M Lassen, A Stadlbauer, ME Mayerhöfer, M Hartenbach, M Hacker, T BeyerA6 High resolution digital FDG PET/MRI imaging for assessment of ACL graft viabilityK Binzel, R Magnussen, W Wei, MU Knopp, DC Flanigan, C Kaeding, MV KnoppA7 Using pre-existing hematotoxicity as predictor for severe side effects and number of treatment cycles of Xofigo therapyA Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A HaugA8 QDOSE - comprehensive software solution for internal dose assessmentWencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas KlugeA9 Clinical impact of Time-of-Flight on next-generation digital PET imaging of Yttrium-90 radioactivity following liver radioembolizationCL Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, MV KnoppA10 Snakes in patients! Lessons learned from programming active contours for automated organ segmentationM Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, RP Baum, B Knäusl, D GeorgA11 Influence of a genetic polymorphism on brain uptake of the dual ABCB1/ABCG2 substrate [11C]tariquidarM Bauer, B Wulkersdorfer, W Wadsak, C Philippe, H Haslacher, M Zeitlinger, O LangerA12 Outcome prediction of temporal lobe epilepsy surgery from P-glycoprotein activity...
April 2016: EJNMMI Research
Vladimir López, Margarita Villar, João Queirós, Joaquín Vicente, Lourdes Mateos-Hernández, Iratxe Díez-Delgado, Marinela Contreras, Paulo C Alves, Pilar Alberdi, Christian Gortázar, José de la Fuente
Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection...
March 2016: PLoS Neglected Tropical Diseases
Jorge Castro-Garza, Francisco González-Salazar, Frederick D Quinn, Russell K Karls, Laura Hermila De La Garza-Salinas, Francisco J Guzmán-de la Garza, Javier Vargas-Villarreal
Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate...
January 2016: Revista Argentina de Microbiología
Grant Theron, Rouxjeane Venter, Greg Calligaro, Liezel Smith, Jason Limberis, Richard Meldau, Duncan Chanda, Aliasgar Esmail, Jonny Peter, Keertan Dheda
BACKGROUND: Patients with previous tuberculosis may have residual DNA in sputum that confounds nucleic acid amplification tests such as Xpert MTB/RIF. Little is known about the frequency of Xpert-positive, culture-negative ("false positive") results in retreatment patients, whether these are distinguishable from true positives, and whether Xpert's automated filter-based wash step reduces false positivity by removing residual DNA associated with nonintact cells. METHODS: Pretreatment patients (n = 2889) with symptoms of tuberculosis from Cape Town, South Africa, underwent a sputum-based liquid culture and Xpert...
April 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
N Bhagya, K R Chandrashekar
Stephania tetrandra and other related species of Menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. The plant is extensively referenced in the Chinese Pharmacopoeia for its use in the Chinese medicinal system as an analgesic and diuretic agent and also in the treatment of hypertension and various other ailments, including asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Tetrandrine, well-known to act as a calcium channel blocker, has been tested in clinical trials and found effective against silicosis, hypertension, inflammation and lung cancer without any toxicity...
May 2016: Phytochemistry
Shih-Wei Lee, Lawrence Shih-Hsin Wu, Guan-Mau Huang, Kai-Yao Huang, Tzong-Yi Lee, Julia Tzu-Ya Weng
BACKGROUND: Tuberculosis (TB) is a serious infectious disease in that 90% of those latently infected with Mycobacterium tuberculosis present no symptoms, but possess a 10% lifetime chance of developing active TB. To prevent the spread of the disease, early diagnosis is crucial. However, current methods of detection require improvement in sensitivity, efficiency or specificity. In the present study, we conducted a microarray experiment, comparing the gene expression profiles in the peripheral blood mononuclear cells among individuals with active TB, latent infection, and healthy conditions in a Taiwanese population...
2016: BMC Bioinformatics
Rena Buckstein, Graeme Fraser, Matthew Cheung, Vishal Kukreti, John Kuruvilla, Kevin Imrie, Eugenia Piliotis, Gregory Pond, Jolanta Windsor, Zeina Ghorab, Kevin Shuoprasad, Ruth Turner, Ralph M Meyer, Kathy Pritchard, Scott Walker, Mark Levine, Michael Crump
BACKGROUND: Alemtuzumab has single-agent activity in relapsed peripheral T cell lymphoma (PTL), but the optimal dose and/or schedule in combination with chemotherapy for first-line use is unknown. The primary objectives were to establish the maximally tolerated dose and pharmacokinetics (PK) of alemtuzumab combined in this way. PATIENTS AND METHODS: Adult patients with untreated CD52-positive (CD52(+)) PTL were enrolled in a phase I trial. Alemtuzumab was given subcutaneously in escalating doses and/or schedules in combination with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) using a 3+3 design...
January 2016: Clinical Lymphoma, Myeloma & Leukemia
Lanbo Shi, Hugh Salamon, Eliseo A Eugenin, Richard Pine, Andrea Cooper, Maria L Gennaro
To elucidate the little-known bioenergetic pathways of host immune cells in tuberculosis, a granulomatous disease caused by the intracellular pathogen Mycobacterium tuberculosis, we characterized infected murine lung tissue by transcriptomic profiling and confocal imaging. Transcriptomic analysis revealed changes of host energy metabolism during the course of infection that are characterized by upregulation of key glycolytic enzymes and transporters for glucose uptake, and downregulation of enzymes participating in the tricarboxylic acid cycle and oxidative phosphorylation...
December 10, 2015: Scientific Reports
José de la Fuente, Iratxe Díez-Delgado, Marinela Contreras, Joaquín Vicente, Alejandro Cabezas-Cruz, Raquel Tobes, Marina Manrique, Vladimir López, Beatriz Romero, Javier Bezos, Lucas Dominguez, Iker A Sevilla, Joseba M Garrido, Ramón Juste, Guillermo Madico, Edward Jones-López, Christian Gortazar
Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly affect humans and animals worldwide. The life cycle of mycobacteria is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Recently, comparative genomics analyses have provided new insights into the evolution and adaptation of the MTBC to survive inside the host. However, most of this information has been obtained using M. tuberculosis but not other members of the MTBC such as M...
November 2015: PLoS Neglected Tropical Diseases
Vincenzo Maione, Alessia Ruggiero, Luigi Russo, Alfonso De Simone, Paolo Vincenzo Pedone, Gaetano Malgieri, Rita Berisio, Carla Isernia
Mycobacterium tuberculosis latent infection is maintained for years with no clinical symptoms and no adverse effects for the host. The mechanism through which dormant M. tuberculosis resuscitates and enters the cell cycle leading to tuberculosis is attracting much interest. The RPF family of proteins has been found to be responsible for bacteria resuscitation and normal proliferation. This family of proteins in M. tuberculosis is composed by five homologues (named RpfA-E) and understanding their conformational, structural and functional peculiarities is crucial to the design of therapeutic strategies...
2015: PloS One
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