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Lipid metabolism tuberculosis

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https://www.readbyqxmd.com/read/29908542/mir-1224-expression-is-increased-in-human-macrophages-after-infection-with-bacillus-calmette-gu%C3%A3-rin-bcg
#1
Shamila D Alipoor, Esmaeil Mortaz, Payam Tabarsi, Majid Marjani, Mohammad Varahram, Gert Folkerts, Johan Garssen, Ian M Adcock
Tuberculosis (TB) remains a major threat to human health. Understanding the strategies mycobacteria take to overcome immune defense is important in order to control the infection. Micro (mi)RNAs are master regulators of most pathways in the human body.  Infection with mycobacterium impacts upon the host metabolic pathways as they are subverted to obtain the nutrition for intracellular TB survival. In this study, we aimed to investigate the effect of Bacillus Calmette-Guérin (BCG) infection on the expression of three miRNAs (miR-1224, -484 and -425), which are important in infection and in the regulation of metabolic pathways...
June 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29906645/more-than-cholesterol-catabolism-regulatory-vulnerabilities-in-mycobacterium-tuberculosis
#2
REVIEW
Amber C Bonds, Nicole S Sampson
Mycobacterium tuberculosis (Mtb) is the epitome of persistent. Mtb is the pathogen that causes tuberculosis, the leading cause of death by infection worldwide. The success of this pathogen is due in part to its clever ability to adapt to its host environment and its effective manipulation of the host immune system. A major contributing factor to the survival and virulence of Mtb is its acquisition and metabolism of host derived lipids including cholesterol. Accumulating evidence suggests that the catabolism of cholesterol during infection is highly regulated by cholesterol catabolites...
June 12, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29844505/phospholipid-homeostasis-membrane-tenacity-and-survival-of-mtb-in-lipid-rich-conditions-is-determined-by-mmpl11-function
#3
Ankur Bothra, Prabhakar Arumugam, Vipul Panchal, Dilip Menon, Sonali Srivastava, Deepthi Shankaran, Ananya Nandy, Neetika Jaisinghani, Archana Singh, Rajesh S Gokhale, Sheetal Gandotra, Vivek Rao
The mycobacterial cell wall is a chemically complex array of molecular entities that dictate the pathogenesis of Mycobacterium tuberculosis. Biosynthesis and maintenance of this dynamic entity in mycobacterial physiology is still poorly understood. Here we demonstrate a requirement for M. tuberculosis MmpL11 in the maintenance of the cell wall architecture and stability in response to surface stress. In the presence of a detergent like Tyloxapol, a mmpL11 deletion mutant suffered from a severe growth attenuation as a result of altered membrane polarity, permeability and severe architectural damages...
May 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29844232/biochemical-characterization-of-isoniazid-resistant-mycobacterium-tuberculosis-can-the-analysis-of-clonal-strains-reveal-novel-targetable-pathways
#4
Luisa Maria Nieto R, Carolina Mehaffy, M Nurul Islam, Bryna Fitzgerald, John Belisle, Jessica Prenni, Karen M Dobos
Tuberculosis (TB) continues to be an important public health threat worldwide, due in part to drug resistant Mycobacterium tuberculosis (Mtb) strains. The United States recently reported a shortage of isoniazid (INH) which could drive higher INH resistant rates. Changes in the Mtb proteome before and after acquisition of INH resistance in a clean genetic background remain understudied and may elucidate alternate drug targets. Here, we focused on Mtb clonal strains to characterize the consequences of INH resistance on mycobacterial metabolism...
May 29, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29800702/interactome-analysis-of-rv0148-to-predict-potential-targets-and-their-pathways-linked-to-aminoglycosides-drug-resistance-an-insilico-approach
#5
Divakar Sharma, Rananjay Singh, Nirmala Deo, Deepa Bisht
Failure of multi drug resistant tuberculosis (MDR-TB) treatment has increased the risk of aminoglycosides resistance, disease transmission, morbidity and mortality. Aminoglycosides are commonly used in multi drug resistant tuberculosis (MDR-TB) treatment. They inhibit protein synthesis by interacting with translationary steps. Apart from gene mutations various mechanisms of aminoglycosides resistance have been reported but still our knowledge regarding aminoglycosides resistance is fragmentary. Proteomics and bioinformatics approaches are the most accepted approaches to explore the unrevealed mechanisms of aminoglycosides resistance...
May 23, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29779698/patients-with-concurrent-tuberculosis-and-diabetes-have-a-pro-atherogenic-plasma-lipid-profile
#6
Frank Vrieling, Katharina Ronacher, Léanie Kleynhans, Erik van den Akker, Gerhard Walzl, Tom H M Ottenhoff, Simone A Joosten
BACKGROUND: Type 2 diabetes mellitus (DM) is a major risk factor for development of tuberculosis (TB), however the underlying molecular foundations are unclear. Since lipids play a central role in the development of both DM and TB, lipid metabolism may be important for TB-DM pathophysiology. METHODS: A 1 H NMR spectroscopy-based platform was used to determine 225 lipid and other metabolic intermediates in plasma samples of healthy controls (n = 50) and patients with TB (n = 50), DM (n = 50) or TB-DM (n = 27)...
May 17, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29760207/association-of-mycobacterium-proteins-to-lipid-droplets
#7
Richard M Armstrong, Dominique C Carter, Samantha N Atkinson, Scott S Terhune, Thomas C Zahrt
Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect of its lifecycle is the ability to enter into an altered physiological state of non-replicating persistence during latency and resist elimination by the host immune system. One mechanism by which M. tuberculosis facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are semi-quasi organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins...
May 14, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29718271/cholesterol-and-fatty-acids-grease-the-wheels-of-mycobacterium-tuberculosis-pathogenesis
#8
Kaley M Wilburn, Rachael A Fieweger, Brian C VanderVen
Tuberculosis is a distinctive disease in which the causative agent, Mycobacterium tuberculosis, can persist in humans for decades by avoiding clearance from host immunity. During infection, M. tuberculosis maintains viability by extracting and utilizing essential nutrients from the host, and this is a prerequisite for all of the pathogenic activities that are deployed by the bacterium. In particular, M. tuberculosis preferentially acquires and metabolizes host-derived lipids (fatty acids and cholesterol), and the bacterium utilizes these substrates to cause and maintain disease...
March 1, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29709002/b-cells-response-directed-against-cut4-and-cfp21-lipolytic-enzymes-in-active-and-latent-tuberculosis-infections
#9
Wendy Rénier, Arnaud Bourdin, Pierre-Alain Rubbo, Marianne Peries, Luc Dedieu, Sophie Bendriss, Laurent Kremer, Stéphane Canaan, Dominique Terru, Sylvain Godreuil, Nicolas Nagot, Philippe Van de Perre, Edouard Tuaillon
BACKGROUND: Better understanding of the immune response directed against Mycobacterium tuberculosis (Mtb) is critical for development of vaccine strategies and diagnosis tests. Previous studies suggested that Mtb enzymes involved in lipid metabolism, are associated with persistence and/or reactivation of dormant bacilli. METHODS: Circulating antibodies secreting cells (ASCs), memory B cells, and antibodies directed against Cut4 (Rv3452) and CFP21 (Rv1984c) antigens were explored in subjects with either active- or latent-tuberculosis (LTB), and in Mtb-uninfected individuals...
2018: PloS One
https://www.readbyqxmd.com/read/29675017/-de-novo-fatty-acid-synthesis-during-mycobacterial-infection-is-a-prerequisite-for-the-function-of-highly-proliferative-t-cells-but-not-for-dendritic-cells-or-macrophages
#10
Philipp Stüve, Lucía Minarrieta, Hanna Erdmann, Catharina Arnold-Schrauf, Maxine Swallow, Melanie Guderian, Freyja Krull, Alexandra Hölscher, Peyman Ghorbani, Jochen Behrends, Wolf-Rainer Abraham, Christoph Hölscher, Tim D Sparwasser, Luciana Berod
Mycobacterium tuberculosis ( Mtb ), the causative agent of human tuberculosis, is able to efficiently manipulate the host immune system establishing chronic infection, yet the underlying mechanisms of immune evasion are not fully understood. Evidence suggests that this pathogen interferes with host cell lipid metabolism to ensure its persistence. Fatty acid metabolism is regulated by acetyl-CoA carboxylase (ACC) 1 and 2; both isoforms catalyze the conversion of acetyl-CoA into malonyl-CoA, but have distinct roles...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29668262/visualization-of-mycobacterial-biomarkers-and-tuberculosis-drugs-in-infected-tissue-by-maldi-ms-imaging
#11
Landry Blanc, Anne Lenaerts, Véronique Dartois, Brendan Prideaux
MALDI mass-spectrometry imaging (MALDI-MSI) is a technique capable of the label-free identification and visualization of analytes in tissue sections. We have previously applied MALDI-MSI to the study of the spatial distribution of tuberculosis (TB) drugs in necrotic lung granulomas characteristic of pulmonary TB disease, revealing heterogeneous and often suboptimal drug distributions. To investigate the impact of differential drug distributions at sites of infection, we sought to image mycobacterial biomarkers to coregister drugs and bacteria in lesion sections...
May 15, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29663798/avoiding-antibiotic-inactivation-in-mycobacterium-tuberculosis-by-rv3406-through-strategic-nucleoside-modification
#12
Matthew R Bockman, Curtis A Engelhart, Surendra Dawadi, Peter Larson, Divya Tiwari, David M Ferguson, Dirk Schnappinger, Courtney C Aldrich
5'-[ N-(d-biotinoyl)sulfamoyl]amino-5'-deoxyadenosine (Bio-AMS, 1) possesses selective activity against Mycobacterium tuberculosis ( Mtb) and arrests fatty acid and lipid biosynthesis through inhibition of the Mycobacterium tuberculosis biotin protein ligase ( MtBPL). Mtb develops spontaneous resistance to 1 with a frequency of at least 1 × 10-7 by overexpression of Rv3406, a type II sulfatase that enzymatically inactivates 1. In an effort to circumvent this resistance mechanism, we describe herein strategic modification of the nucleoside at the 5'-position to prevent enzymatic inactivation...
April 17, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29648787/measuring-the-global-substrate-specificity-of-mycobacterial-serine-hydrolases-using-a-library-of-fluorogenic-ester-substrates
#13
Braden Bassett, Brent Waibel, Alex White, Heather Hansen, Dominique Stephens, Andrew Koelper, Erik M Larsen, Charles Kim, Adam Glanzer, Luke D Lavis, Geoffrey C Hoops, R Jeremy Johnson
Among the proteins required for lipid metabolism in Mycobacterium tuberculosis are a significant number of uncharacterized serine hydrolases, especially lipases and esterases. Using a streamlined synthetic method, a library of immolative fluorogenic ester substrates was expanded to better represent the natural lipidomic diversity of Mycobacterium. This expanded fluorogenic library was then used to rapidly characterize the global structure activity relationship (SAR) of mycobacterial serine hydrolases in M. smegmatis under different growth conditions...
June 8, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29593722/formation-of-foamy-macrophages-by-tuberculous-pleural-effusions-is-triggered-by-the-interleukin-10-signal-transducer-and-activator-of-transcription-3-axis-through-acat-upregulation
#14
Melanie Genoula, José Luis Marín Franco, Maeva Dupont, Denise Kviatcovsky, Ayelén Milillo, Pablo Schierloh, Eduardo Jose Moraña, Susana Poggi, Domingo Palmero, Dulce Mata-Espinosa, Erika González-Domínguez, Juan Carlos León Contreras, Paula Barrionuevo, Bárbara Rearte, Marlina Olyissa Córdoba Moreno, Adriana Fontanals, Agostina Crotta Asis, Gabriela Gago, Céline Cougoule, Olivier Neyrolles, Isabelle Maridonneau-Parini, Carmen Sánchez-Torres, Rogelio Hernández-Pando, Christel Vérollet, Geanncarlo Lugo-Villarino, María Del Carmen Sasiain, Luciana Balboa
The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29573124/the-role-of-lipids-in-host-pathogen-interactions
#15
REVIEW
Glenn F W Walpole, Sergio Grinstein, Johannes Westman
Innate immunity relies on the effective recognition and elimination of pathogenic microorganisms. This entails sequestration of pathogens into phagosomes that promptly acquire microbicidal and degradative properties. This complex series of events, which involve cytoskeletal reorganization, membrane remodeling and the activation of multiple enzymes, is orchestrated by lipid signaling. To overcome this immune response, intracellular pathogens acquired mechanisms to subvert phosphoinositide-mediated signaling and use host lipids, notably cholesterol, as nutrients...
May 2018: IUBMB Life
https://www.readbyqxmd.com/read/29524441/modelling-the-effects-of-bacterial-cell-state-and-spatial-location-on-tuberculosis-treatment-insights-from-a-hybrid-multiscale-cellular-automaton-model
#16
Ruth Bowness, Mark A J Chaplain, Gibin G Powathil, Stephen H Gillespie
If improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of different compounds into lesions. Treatment success therefore depends critically on the responses of the individual bacteria that constitute the infection. We propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the cellular level, linking the behaviour of individual bacteria and host cells with the macroscopic behaviour of the microenvironment...
June 7, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29523332/an-iclr-like-protein-from-mycobacteria-regulates-leucd-operon-and-induces-dormancy-like-growth-arrest-in-mycobacterium-smegmatis
#17
Rajendra Kumar Angara, Suhail Yousuf, Shailesh Kumar Gupta, Akash Ranjan
leuCD operon encodes isopropylmalate isomerase (IPMI), an essential enzyme in leucine biosynthesis. Leucine biosynthesis is one of the essential metabolic pathways for Mycobacterium tuberculosis survival inside the macrophage. In this study, we identified an IclR like transcription regulator, Rv2989 involved in regulation of leuCD expression. Further, we have shown that the Rv2989 binding site overlaps with the promoter region of leuCD, indicating its direct involvement in the regulation of this operon. Ectopic expression of Rv2989 in M...
January 2018: Tuberculosis
https://www.readbyqxmd.com/read/29485123/triacylglycerol-nourishing-molecule-in-endurance-of-mycobacterium-tuberculosis
#18
Pratap C Mali, Laxman S Meena
The ability of Mycobacterium tuberculosis (M. tuberculosis) to accumulate lipid-rich molecules as an energy source obtained from host cell debris remains interesting. Additionally, the potential of M. tuberculosis to survive under different stress conditions leading to its dormant state in pathogenesis remains elusive. The exact mechanism by which these lipid bodies generated in M. tuberculosis infection and utilized by bacilli inside infected macrophage for its survival is still not understood. In this, during bacillary infection, many metabolic pathways are involved that influence the survival of M...
March 2018: Journal of Biosciences
https://www.readbyqxmd.com/read/29475946/the-anaplerotic-node-is-essential-for-the-intracellular-survival-of-mycobacterium-tuberculosis
#19
Piyali Basu, Noor Sandhu, Apoorva Bhatt, Albel Singh, Ricardo Balhana, Irene Gobe, Nicola A Crowhurst, Tom A Mendum, Liang Gao, Jane L Ward, Michael H Beale, Johnjoe McFadden, Dany J V Beste
Enzymes at the phosphoenolpyruvate (PEP)-pyruvate-oxaloacetate or anaplerotic (ANA) node control the metabolic flux to glycolysis, gluconeogenesis, and anaplerosis. Here we used genetic, biochemical, and 13 C isotopomer analysis to characterize the role of the enzymes at the ANA node in intracellular survival of the world's most successful bacterial pathogen, Mycobacterium tuberculosis ( Mtb ). We show that each of the four ANA enzymes, pyruvate carboxylase (PCA), PEP carboxykinase (PCK), malic enzyme (MEZ), and pyruvate phosphate dikinase (PPDK), performs a unique and essential metabolic function during the intracellular survival of Mtb...
April 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29472294/impact-of-the-epoxide-hydrolase-ephd-on-the-metabolism-of-mycolic-acids-in-mycobacteria
#20
Jan Madacki, Françoise Laval, Anna Grzegorzewicz, Anne Lemassu, Monika Záhorszká, Michael Arand, Michael McNeil, Mamadou Daffé, Mary Jackson, Marie-Antoinette Lanéelle, Jana Korduláková
Mycolic acids are the hallmark of the cell envelope in mycobacteria, which include the important human pathogens Mycobacterium tuberculosis and Mycobacterium leprae Mycolic acids are very long C60-C90 α-alkyl β-hydroxy fatty acids having a variety of functional groups on their hydrocarbon chain that define several mycolate types. Mycobacteria also produce an unusually large number of putative epoxide hydrolases, but the physiological functions of these enzymes are still unclear. Here, we report that the mycobacterial epoxide hydrolase EphD is involved in mycolic acid metabolism...
April 6, 2018: Journal of Biological Chemistry
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