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Lipid metabolism tuberculosis

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https://www.readbyqxmd.com/read/29388150/rv0646c-an-esterase-from-m-tuberculosis-up-regulates-the-host-immune-response-in-thp-1-macrophages-cells
#1
Ruchi Rastogi, Arbind Kumar, Jagdeep Kaur, Varinder Saini, Jasbinder Kaur, Archana Bhatnagar
The genome sequence of Mycobacterium tuberculosis revealed the presence of several hydrolases involved in lipid metabolism including the members of Lip gene family. Rv0646c (LipG) is one of them. It is annotated as putative esterase/lipase because of the presence of consensus sequence 'GXSXG.' The gene was cloned, expressed, and purified in E. coli. It showed 22 U/mg specific activity with pNP-butyrate as a preferred substrate. However, it actively worked on substrates with short chain. The enzyme was optimally active at 50 °C/pH 8...
January 31, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29345343/mycobacterium-tuberculosis-rewiring-host-cell-signaling-to-promote-infection
#2
REVIEW
Michael D Stutz, Michelle P Clark, Marcel Doerflinger, Marc Pellegrini
The ability of Mycobacterium tuberculosis to cause disease hinges upon successfully thwarting the innate defenses of the macrophage host cell. The pathogen's trump card is its armory of virulence factors that throw normal host cell signaling into disarray. This process of subverting the macrophage begins upon entry into the cell, when M. tuberculosis actively inhibits the fusion of the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array of host signal transduction pathways, which dampens the macrophage's host-protective cytokine response, while simultaneously adapting host cell metabolism to stimulate lipid body accumulation...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29301937/cyclipostins-and-cyclophostin-analogs-inhibit-the-antigen-85c-from-mycobacterium-tuberculosis-both-in-vitro-and-in-vivo
#3
Albertus Viljoen, Matthias Richard, Phuong Chi Nguyen, Patrick Fourquet, Luc Camoin, Rishi R Paudal, Giri R Gnawali, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan, Mickael Blaise, Laurent Kremer
An increasing prevalence of cases of drug-resistant tuberculosis requires the development of more efficacious chemotherapies. We previously reported the discovery of a new class of Cyclipostins and Cyclophostin (CyC) analogs exhibiting potent activity against Mycobacterium tuberculosis both in vitro and in infected macrophages. Competitive labeling/enrichment assays combined with MS have identified several serine or cysteine enzymes in lipid and cell wall metabolism as putative targets of these CyC compounds...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29247215/the-transcriptome-of-mycobacterium-tuberculosis-in-a-lipid-rich-dormancy-model-through-rnaseq-analysis
#4
Diana A Aguilar-Ayala, Laurentijn Tilleman, Filip Van Nieuwerburgh, Dieter Deforce, Juan Carlos Palomino, Peter Vandamme, Jorge A Gonzalez-Y-Merchand, Anandi Martin
Tuberculosis (TB) is currently the number one killer among infectious diseases worldwide. Lipids are abundant molecules during the infectious cycle of Mycobacterium tuberculosis (Mtb) and studies better mimicking its actual metabolic state during pathogenesis are needed. Though most studies have focused on the mycobacterial lipid metabolism under standard culture conditions, little is known about the transcriptome of Mtb in a lipid environment. Here we determined the transcriptome of Mtb H37Rv in a lipid-rich environment (cholesterol and fatty acid) under aerobic and hypoxic conditions, using RNAseq...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29245963/identification-of-potential-metabolic-biomarkers-of-cerebrospinal-fluids-that-differentiate-tuberculous-meningitis-from-other-types-of-meningitis-by-a-metabolomics-study
#5
Yi-Ning Dai, Hai-Jun Huang, Wen-Yuan Song, Yong-Xi Tong, Dan-Hong Yang, Ming-Shan Wang, Yi-Cheng Huang, Mei-Juan Chen, Jia-Jie Zhang, Ze-Ze Ren, Wei Zheng, Hong-Ying Pan
Tuberculous meningitis (TBM) is caused by tuberculosis infection of of the meninges, which are the membrane systems that encircle the brain, with a high morbidity and mortality rate. It is challenging to diagnose TBM among other types of meningitis, such as viral meningitis, bacterial meningitis and cryptococcal meningitis. We aimed to identify metabolites that are differentially expressed between TBM and the other types of meningitis by a global metabolomics analysis. The cerebrospinal fluids (CSF) from 50 patients with TBM, 17 with viral meningitis, 17 with bacterial meningitis, and 16 with cryptococcal meningitis were analyzed using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS)...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29208413/characterization-of-ml0314c-of-mycobacterium-leprae-and-deciphering-its-role-in-the-immune-response-in-leprosy-patients
#6
Gurkamajit Kaur, Aashish Sharma, Tarun Narang, Sunil Dogra, Jagdeep Kaur
Mycobacterium leprae has a reduced genome size due to the reductive evolution over a long period of time. Lipid metabolism plays an important role in the life cycle and pathogenesis of this bacterium. In comparison to 26 lip genes (Lip A-Z) of M. tuberculosis, M. leprae retained only three orthologs indicating their importance in its life cycle. ML0314c (LipU) is one of them. It is conserved throughout the mycobacterium species. Bioinformatics analysis showed the presence of an α/β hydrolase fold and 'GXSXG' characteristic of the esterases/lipases...
December 2, 2017: Gene
https://www.readbyqxmd.com/read/29190491/lipid-metabolism-and-its-implication-in-mycobacteria-host-interaction
#7
REVIEW
Gabriela Gago, Lautaro Diacovich, Hugo Gramajo
The complex lipids present in the cell wall of Mycobacterium tuberculosis (Mtb) act as major effector molecules that actively interact with the host, modulating its metabolism and stimulating the immune response, which in turn affects the physiology of both, the host cell and the bacilli. Lipids from the host are also nutrient sources for the pathogen and define the fate of the infection by modulating lipid homeostasis. Although new technologies and experimental models of infection have greatly helped understanding the different aspects of the host-pathogen interactions at the lipid level, the impact of this interaction in the Mtb lipid regulation is still incipient, mainly because of the low background knowledge in this area of research...
November 27, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29143876/deregulation-of-genes-associated-with-alternate-drug-resistance-mechanisms-in-mycobacterium-tuberculosis
#8
Kalpana Sriraman, Kayzad Nilgiriwala, Dhananjaya Saranath, Anirvan Chatterjee, Nerges Mistry
Alternate mechanisms of drug resistance involving intrinsic defense pathways play an important role in development of drug resistance. Deregulation of drug efflux, cellular metabolism, and DNA repair have been indicated to have effect on drug tolerance and persistence. Here we chose eight genes from these pathways to investigate their association with development of multidrug resistance (MDR). We generated mono drug resistant and MDR strains of rifampicin and isoniazid and examined the differential expression of genes belonging to efflux, DNA repair and cell wall lipid synthesis pathways...
November 16, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29067283/small-molecule-mediated-restoration-of-mitochondrial-function-augments-anti-mycobacterial-activity-of-human-macrophages-subjected-to-cholesterol-induced-asymptomatic-dyslipidemia
#9
Suman Asalla, Krishnaveni Mohareer, Sharmistha Banerjee
Mycobacterium tuberculosis (M.tb) infection manifests into tuberculosis (TB) in a small fraction of the infected population that comprises the TB susceptible group. Identifying the factors potentiating susceptibility to TB persistence is one of the prime agenda of TB control programs. Recently, WHO recognized diabetes as a risk factor for TB disease progression. The closely related pathological state of metabolic imbalance, dyslipidemia, is yet another emerging risk factor involving deregulation in host immune responses...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28988960/pdim-and-sl1-accumulation-in-mycobacterium-tuberculosis-is-associated-with-mce4a-expression
#10
Pooja Singh, Rajesh Sinha, Gaurav Tyagi, Naresh Kumar Sharma, Neeraj K Saini, Amita Chandolia, Ashok Kumar Prasad, Mandira Varma-Basil, Mridula Bose
Lipid metabolism forms the heart and soul of Mycobacterium tuberculosis life cycle. Starting from macrophage invasion at cholesterol rich micro-domains to a sustainable survival for infection by utilizing cholesterol, Mycobacterium displays the nexus of metabolic pathways around host derived lipids. mce4 operon acts as cholesterol import system in M. tuberculosis and here we demonstrate role of mce4A gene of this operon in cholesterol catabolism. Here M. tuberculosis H37Rv overexpressing Rv3499c (mce4A) recombinant was used as a model to decipher the metabolic flux during intake and utilization of host lipids by mycobacteria...
October 5, 2017: Gene
https://www.readbyqxmd.com/read/28961957/identification-of-novel-mutations-associated-with-cycloserine-resistance-in-mycobacterium-tuberculosis
#11
Jiazhen Chen, Shuo Zhang, Peng Cui, Wanliang Shi, Wenhong Zhang, Ying Zhang
Objectives: d -Cycloserine is an important second-line drug used to treat MDR- and XDR-TB. However, the mechanisms of resistance to d -cycloserine are not well understood. Here we investigated the molecular basis of d -cycloserine resistance using in vitro -isolated resistant mutants. Methods: Mycobacterium tuberculosis H37Rv was subjected to mutant selection on 7H11 agar plates containing varying concentrations of d -cycloserine. A total of 18 d -cycloserine-resistant mutants were isolated and subjected to WGS...
September 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28924204/cyclipostins-and-cyclophostin-analogs-as-promising-compounds-in-the-fight-against-tuberculosis
#12
Phuong Chi Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin P Martin, Rishi Paudel, Giri R Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan
A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC50 = 500 nM)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852109/label-free-optical-vibrational-spectroscopy-to-detect-the-metabolic-state-of-m-tuberculosis-cells-at-the-site-of-disease
#13
Vincent O Baron, Mingzhou Chen, Simon O Clark, Ann Williams, Robert J H Hammond, Kishan Dholakia, Stephen H Gillespie
Tuberculosis relapse is a barrier to shorter treatment. It is thought that lipid rich cells, phenotypically resistant to antibiotics, may play a major role. Most studies investigating relapse use sputum samples although tissue bacteria may play an important role. We developed a non-destructive, label-free technique combining wavelength modulated Raman (WMR) spectroscopy and fluorescence detection (Nile Red staining) to interrogate Mycobacterium tuberculosis cell state. This approach could differentiate single "dormant" (lipid rich, LR) and "non-dormant" (lipid poor, LP) cells with high sensitivity and specificity...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28655597/identification-of-host-proteins-predictive-of-early-stage-mycobacterium-tuberculosis-infection
#14
Charles M Bark, Ameur M Manceur, LaShaunda L Malone, Mary Nsereko, Brenda Okware, Harriet K Mayanja, Moses L Joloba, Isabelle Rajotte, Marija Mentinova, Phyla Kay, Seydina Lo, Patrick Tremblay, Catherine M Stein, W Henry Boom, Eustache Paramithiotis
The objective of this study was to identify blood-based protein biomarkers of early stage Mycobacterium tuberculosis (Mtb) infection. We utilized plasma and serum specimens from TB patients and their contacts (age≥12) enrolled in a household contact study in Uganda. In the discovery phase cross-sectional samples from 104 HIV-uninfected persons classified as either active TB, latent Mtb infection (LTBI), tuberculin skin test (TST) converters, or persistent TST-negative were analyzed. Two hundred eighty-nine statistically significant (false discovery rate corrected p<0...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#15
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...
July 18, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28627685/metabolomic-analysis-based-on-1h-nuclear-magnetic-resonance-spectroscopy-metabolic-profiles-in-tuberculous-malignant-and-transudative-pleural-effusion
#16
Cheng Wang, Jingjin Peng, Yanling Kuang, Jiaqiang Zhang, Luming Dai
Pleural effusion is a common clinical manifestation with various causes. Current diagnostic and therapeutic methods have exhibited numerous limitations. By involving the analysis of dynamic changes in low molecular weight catabolites, metabolomics has been widely applied in various types of disease and have provided platforms to distinguish many novel biomarkers. However, to the best of our knowledge, there are few studies regarding the metabolic profiling for pleural effusion. In the current study, 58 pleural effusion samples were collected, among which 20 were malignant pleural effusions, 20 were tuberculous pleural effusions and 18 were transudative pleural effusions...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#17
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
August 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28587792/breaking-fat-how-mycobacteria-and-other-intracellular-pathogens-manipulate-host-lipid-droplets
#18
REVIEW
Caroline Barisch, Thierry Soldati
Tuberculosis (Tb) is a lung infection caused by Mycobacterium tuberculosis (Mtb). With one third of the world population latently infected, it represents the most prevalent bacterial infectious diseases worldwide. Typically, persistence is linked to so-called "dormant" slow-growing bacteria, which have a low metabolic rate and a reduced response to antibiotic treatments. However, dormant bacteria regain growth and virulence when the immune system is weakened, leading again to the active form of the disease...
June 3, 2017: Biochimie
https://www.readbyqxmd.com/read/28535936/lipids-in-infectious-diseases-the-case-of-aids-and-tuberculosis
#19
REVIEW
Fabrice Dumas, Evert Haanappel
Lipids play a central role in many infectious diseases. AIDS (Acquired Immune Deficiency Syndrome) and tuberculosis are two of the deadliest infectious diseases to have struck mankind. The pathogens responsible for these diseases, Human Immunodeficiency Virus-1 and Mycobacterium tuberculosis, rely on lipids and on lipid membrane properties to gain access to their host cells, to persist in them and ultimately to egress from their hosts. In this Review, we discuss the life cycles of these pathogens and the roles played by lipids and membranes...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#20
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
October 2017: Human Cell
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