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Lipid metabolism tuberculosis

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https://www.readbyqxmd.com/read/28988960/pdim-and-sl1-accumulation-in-mycobacterium-tuberculosis-is-associated-with-mce4a-expression
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28522365/knowns-and-unknowns-of-membrane-lipid-synthesis-in-streptomycetes
#12
Mario Sandoval-Calderón, Ziqiang Guan, Christian Sohlenkamp
Bacteria belonging to the genus Streptomyces are among the most prolific producers of antibiotics. Research on cellular membrane biosynthesis and turnover is lagging behind in Streptomyces compared to related organisms like Mycobacterium tuberculosis. While natural products discovery in Streptomyces is evidently a priority in order to discover new antibiotics to combat the increase in antibiotic resistant pathogens, a better understanding of this cellular compartment should provide insights into the interplay between core and secondary metabolism...
October 2017: Biochimie
https://www.readbyqxmd.com/read/28475832/a-phenotypic-based-target-screening-approach-delivers-new-antitubercular-ctp-synthetase-inhibitors
#13
Marta Esposito, Sára Szadocka, Giulia Degiacomi, Beatrice S Orena, Giorgia Mori, Valentina Piano, Francesca Boldrin, Júlia Zemanová, Stanislav Huszár, David Barros, Sean Ekins, Joel Lelièvre, Riccardo Manganelli, Andrea Mattevi, Maria Rosalia Pasca, Giovanna Riccardi, Lluis Ballell, Katarína Mikušová, Laurent R Chiarelli
Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds...
June 9, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28419200/switching-to-efavirenz-versus-remaining-on-ritonavir-boosted-lopinavir-in-human-immunodeficiency-virus-infected-children-exposed-to-nevirapine-long-term-outcomes-of-a-randomized-trial
#14
Pamela M Murnane, Renate Strehlau, Stephanie Shiau, Faeezah Patel, Ndileke Mbete, Gillian Hunt, Elaine J Abrams, Ashraf Coovadia, Louise Kuhn
Background: We previously demonstrated the noninferiority of switching to efavirenz (EFV) versus remaining on ritonavir-boosted lopinavir (LPV/r) for virologic control in children infected with human immunodeficiency virus (HIV) and exposed to nevirapine (NVP) for prevention of mother-to-child transmission. Here we assess outcomes up to 4 years post-randomization. Methods: From 2010-2013, 298 NVP-exposed HIV-infected children ≥3 years of age were randomized to switch to EFV or remain on LPV/r in Johannesburg, South Africa (Clinicaltrials...
August 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28412202/the-immunosuppressive-effects-of-a-novel-recombinant-lipq-rv2485c-protein-of-mycobacterium-tuberculosis-on-human-macrophage-cell-lines
#15
Anjani Kumar, Manisha, Gurkamaljit Kaur Sangha, Anju Shrivastava, Jagdeep Kaur
Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28364349/effect-of-blood-biochemical-factors-on-nontraumatic-necrosis-of-the-femoral-head-logistic-regression-analysis
#16
Ying Zhang, Ruibo Sun, Leilei Zhang, Lizhi Feng, Youwen Liu
OBJECTIVE: This case-control study aimed to identify the risk factors of nontraumatic necrosis of the femoral head (NONFH). METHODS: In all, 242 patients with NONFH treated at the hip disease research center of our hospital between March 2012 and October 2015 were included. After excluding 19 patients with tumor or tuberculosis, 223 patients were enrolled. Controls comprised 223 healthy persons selected from our hospital database. Single-factor variance analysis and t test were performed to select the index of statistical significance...
March 31, 2017: Der Orthopäde
https://www.readbyqxmd.com/read/28338924/a-nonsynonymous-snp-catalog-of-mycobacterium-tuberculosis-virulence-genes-and-its-use-for-detecting-new-potentially-virulent-sublineages
#17
Natalya E Mikheecheva, Marina V Zaychikova, Alexander V Melerzanov, Valery N Danilenko
Mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an M. tuberculosis classification approach based on functional polymorphisms in virulence genes. An M. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin-antitoxin systems...
April 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28337966/acid-fast-positive-and-acid-fast-negative-mycobacterium-tuberculosis-the-koch-paradox
#18
REVIEW
Catherine Vilchèze, Laurent Kremer
Acid-fast (AF) staining, also known as Ziehl-Neelsen stain microscopic detection, developed over a century ago, is even today the most widely used diagnostic method for tuberculosis. Herein we present a short historical review of the evolution of AF staining methods and discuss Koch's paradox, in which non-AF tubercle bacilli can be detected in tuberculosis patients or in experimentally infected animals. The conversion of Mycobacterium tuberculosis from an actively growing, AF-positive form to a nonreplicating, AF-negative form during the course of infection is now well documented...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28327797/bacterial-immunostat-mycobacterium-tuberculosis-lipids-and-their-role-in-the-host-immune-response
#19
REVIEW
Adriano Queiroz, Lee W Riley
The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the long-term bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans) trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose) appear to dampen the immune responses...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28327423/characterization-of-an-extracellular-protein-rv1076-from-m-tuberculosis-with-a-potential-role-in-humoral-response
#20
Gurkamaljit Kaur, Varinder Saini, Bandana Kumari, Jasbinder Kaur, Jagdeep Kaur
Many mycobacterial proteins involved in lipid metabolism are reported to be essential for survival and pathogenesis of M. tuberculosis. Rv1076 of M. tuberculosis has been annotated as a putative esterase/lipase based on the consensus sequence 'GXSXG'. It is conserved in all the mycobacterial species. Therefore, in the present study we have characterized Rv1076 gene product in detail. The gene rv1076 was expressed in E. coli and purified from inclusion bodies with approx. 40% yield. The protein showed high specific activity with pNP- butyrate as preferred substrate...
August 2017: International Journal of Biological Macromolecules
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