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Lipid metabolism tuberculosis

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https://www.readbyqxmd.com/read/28327797/bacterial-immunostat-mycobacterium-tuberculosis-lipids-and-their-role-in-the-host-immune-response
#1
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
#2
Gurkamaljit Kaur, Bandana Kumari, 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...
March 19, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28280303/in-silico-discovery-and-in-vitro-activity-of-inhibitors-against-mycobacterium-tuberculosis-7-8-diaminopelargonic-acid-synthase-mtb-bioa
#3
Junie B Billones, Maria Constancia O Carrillo, Voltaire G Organo, Jamie Bernadette A Sy, Nina Abigail B Clavio, Stephani Joy Y Macalino, Inno A Emnacen, Alexandra P Lee, Paul Kenny L Ko, Gisela P Concepcion
Computer-aided drug discovery and development approaches such as virtual screening, molecular docking, and in silico drug property calculations have been utilized in this effort to discover new lead compounds against tuberculosis. The enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in Mycobacterium tuberculosis (Mtb), primarily involved in the lipid biosynthesis pathway, was chosen as the drug target due to the fact that humans are not capable of synthesizing biotin endogenously. The computational screening of 4...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28210262/morphoproteomic-guided-host-directed-therapy-for-tuberculosis
#4
Robert E Brown, Robert L Hunter, Shen-An Hwang
In an effort to develop more effective therapy for tuberculosis (TB), research efforts are looking toward host-directed therapy, reprograming the body's natural defenses to better control the infection. While significant progress is being made, the efforts are limited by lack of understanding of the pathology and pathogenesis of adult type TB disease. We have recently published evidence that the developing lesions in human lungs are focal endogenous lipid pneumonia that constitutes a region of local susceptibility in a person with strong systemic immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28137234/mycobacterial-dna-replication-as-a-target-for-antituberculosis-drug-discovery
#5
Renata Płocińska, Małgorzata Korycka-Machała, Przemysław Płociński, Jarosław Dziadek
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28103313/mycobacterium-marinum-degrades-both-triacylglycerols-and-phospholipids-from-its-dictyostelium-host-to-synthesise-its-own-triacylglycerols-and-generate-lipid-inclusions
#6
Caroline Barisch, Thierry Soldati
During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28062754/mycobacterium-tuberculosis-complex-exhibits-lineage-specific-variations-affecting-protein-ductility-and-epitope-recognition
#7
Inmaculada Yruela, Bruno Contreras-Moreira, Carlos Magalhães, Nuno S Osório, Jesús Gonzalo-Asensio
The advent of whole-genome sequencing has provided an unprecedented detail about the evolution and genetic significance of species-specific variations across the whole Mycobacterium tuberculosis Complex. However, little attention has been focused on understanding the functional roles of these variations in the protein coding sequences. In this work, we compare the coding sequences from 74 sequenced mycobacterial species including M. africanum, M. bovis, M. canettii, M. caprae, M. orygis, and M. tuberculosis Results show that albeit protein variations affect all functional classes, those proteins involved in lipid and intermediary metabolism and respiration have accumulated mutations during evolution...
January 6, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28043593/new-approaches-in-drug-treatment-for-tuberculosis-inhalation-using-liposomes-only-a-future-vision-or-soon-in-clinical-practice
#8
Lars-Olof Larsson
A major change of therapy in respiratory medicine has been the transition from oral or parenteral to inhalation therapy, for example, in asthma. Inhalation of anti-infectious drugs has however not a key-role in the treatment of pulmonary infections such as tuberculosis (TB). The inhalation therapy provides several benefits; the target is reached directly with evasion of first-pass metabolism, thereby resulting in reduced systemic side effects. Furthermore, the drug is delivered to an extensive surface area that is rich in lymphoid tissue...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28002883/cholesterol-metabolism-a-potential-therapeutic-target-in-mycobacteria
#9
REVIEW
Areej Abuhammad
Tuberculosis (TB), although a curable disease, has remained one of the most difficult infections to treat. Mycobacterium tuberculosis (M. tuberculosis.) infects 10 million people worldwide and kills 1.5 million people each year. Reactivation of latent infection is the major cause of TB. Cholesterol is a critical carbon source during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into lipid virulence factors. The M. tuberculosis genome contains a large regulon of cholesterol catabolic genes suggesting that the microorganism can utilise host sterol for infection and persistence...
December 21, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27936614/structural-basis-for-the-strict-substrate-selectivity-of-the-mycobacterial-hydrolase-lipw
#10
Magy G McKary, Jan Abendroth, Thomas E Edwards, R Jeremy Johnson
The complex life cycle of Mycobacterium tuberculosis requires diverse energy mobilization and utilization strategies facilitated by a battery of lipid metabolism enzymes. Among lipid metabolism enzymes, the Lip family of mycobacterial serine hydrolases is essential to lipid scavenging, metabolic cycles, and reactivation from dormancy. On the basis of the homologous rescue strategy for mycobacterial drug targets, we have characterized the three-dimensional structure of full length LipW from Mycobacterium marinum, the first structure of a catalytically active Lip family member...
December 27, 2016: Biochemistry
https://www.readbyqxmd.com/read/27793104/n-acetyl-cysteine-exhibits-potent-anti-mycobacterial-activity-in-addition-to-its-known-anti-oxidative-functions
#11
Eduardo P Amaral, Elisabete L Conceição, Diego L Costa, Michael S Rocha, Jamocyr M Marinho, Marcelo Cordeiro-Santos, Maria Regina D'Império-Lima, Theolis Barbosa, Alan Sher, Bruno B Andrade
BACKGROUND: Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. METHODS: Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals...
October 28, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27769937/secretome-profiling-of-highly-virulent-mycobacterium-bovis-04-303-strain-reveals-higher-abundance-of-virulence-associated-proteins
#12
Fernando Vargas-Romero, Guillermo Mendoza-Hernández, Francisco Suárez-Güemes, Rogelio Hernández-Pando, Mauricio Castañón-Arreola
Mycobacterium bovis is the causative agent of tuberculosis in farms, wildlife and causes sporadic disease in humans. Despite the high similitude in genome sequence between M. bovis strains, some strains like the wild boar 04-303 isolate show a highly virulent phenotype in animal models. Comparative studies will contribute to link protein expression with the virulence phenotype. In vitro, the 04-303 strain was more phagocytized by J774A.1 macrophages in comparison with 444 strain (a cow isolate with the same genotype) and BCG...
November 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27718364/uptake-and-metabolism-of-fluorescent-steroids-by-mycobacterial-cells
#13
Yaroslav Faletrov, Anna Brzostek, Renata Plocinska, Jarosław Dziadek, Elena Rudaya, Irina Edimecheva, Vladimir Shkumatov
Fluorescent steroids BODIPY-cholesterol (BPCh) and 7-nitrobenzoxadiazole-4-amino-(NBD)-labeled 22-NBD-chelesterol (22NC) as well as synthesized 20-(NBD)-pregn-5-en-3β-ol (20NP) were found to undergo bioconversions by Mycobacterium tuberculosis H37Rv and M. smegmatis mc(2) 155. The major fluorescent products were determined to be 4-en-3-one derivatives of the compounds. Degradation of NBD fluorophore was also detected in the cases of 22NC and 20NP, but neither NBD degradation nor steroidal part modification were observed for the synthesized 3-(NBD)-cholestane...
January 2017: Steroids
https://www.readbyqxmd.com/read/27630619/transcriptional-and-physiological-changes-during-mycobacterium-tuberculosis-reactivation-from-non-replicating-persistence
#14
Peicheng Du, Charles D Sohaskey, Lanbo Shi
Mycobacterium tuberculosis can persist for years in the hostile environment of the host in a non-replicating or slowly replicating state. While active disease predominantly results from reactivation of a latent infection, the molecular mechanisms of M. tuberculosis reactivation are still poorly understood. We characterized the physiology and global transcriptomic profiles of M. tuberculosis during reactivation from hypoxia-induced non-replicating persistence. We found that M. tuberculosis reactivation upon reaeration was associated with a lag phase, in which the recovery of cellular physiological and metabolic functions preceded the resumption of cell replication...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27553417/dissecting-host-factors-that-regulate-the-early-stages-of-tuberculosis-infection
#15
Neha Agrawal, Chandrika Bhattacharyya, Ankur Mukherjee, Ubaid Ullah, Bhaswati Pandit, Kanury V S Rao, Partha P Majumder
Incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days...
September 2016: Tuberculosis
https://www.readbyqxmd.com/read/27545345/proteomic-and-morphological-changes-produced-by-subinhibitory-concentration-of-isoniazid-in-mycobacterium-tuberculosis
#16
Paula Az Campanerut-Sá, Luciana D Ghiraldi-Lopes, Jean E Meneguello, Adriana Fiorini, Geisa Pc Evaristo, Vera Ld Siqueira, Regiane Bl Scodro, Eliana V Patussi, Lucélia Donatti, Emanuel M Souza, Rosilene F Cardoso
AIM: To study the proteomic and morphological changes in Mycobacterium tuberculosis H37Rv exposed to subinhibitory concentration of isoniazid (INH). MATERIALS & METHODS: The bacillus was exposed to ½ MIC of INH at 12, 24 and 48 h. The samples' cells were submitted to scanning electron microscopy. The proteins were separated by 2D gel electrophoresis and identified by MS. RESULTS: INH exposure was able to alter the format, the multiplication and causing a cell swelling in the bacillus...
September 2016: Future Microbiology
https://www.readbyqxmd.com/read/27480283/the-%C3%AE-%C3%AE-hydrolase-fold-proteins-of-mycobacterium-tuberculosis-with-reference-to-their-contribution-to-virulence
#17
Glynis Johnson
The α/β hydrolase fold superfamily is an ancient and widely diversified group of primarily hydrolytic enzymes. In this review, the adaptations of these proteins to the pathogenic lifestyle of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, are examined. Of the 105 α/β hydrolases identified in Mtb, many are associated with lipid metabolism, particularly in the biosynthesis and maintenance of the Mtb's unique cell envelope, as well in the large number of extracellular lipases that are likely responsible for degradation of host lipid material...
July 28, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27474746/inibac-induction-is-vitamin-b12-and-mutab-dependent-in-mycobacterium-marinum
#18
Maikel Boot, Marion Sparrius, Kin Ki Jim, Susanna Commandeur, Alexander Speer, Robert van de Weerd, Wilbert Bitter
Tuberculosis can be treated with a 6-month regimen of antibiotics. Although the targets of most of the first-line antibiotics have been identified, less research has focused on the intrabacterial stress responses that follow upon treatment with antibiotics. Studying the roles of these stress genes may lead to the identification of crucial stress-coping mechanisms that can provide additional drug targets to increase treatment efficacy. A three-gene operon with unknown function that is strongly up-regulated upon treatment with isoniazid and ethambutol is the iniBAC operon...
September 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27430928/-abnormal-lipid-metabolism-and-the-mechanisms-caused-by-tuberculosis-infection
#19
N Dong, Y R Fu, Z J Yi
No abstract text is available yet for this article.
July 2016: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27350398/mycobacteriophage-swu1-gp39-can-potentiate-multiple-antibiotics-against-mycobacterium-via-altering-the-cell-wall-permeability
#20
Qiming Li, Mingliang Zhou, Xiangyu Fan, Jianlong Yan, Weimin Li, Jianping Xie
M. tuberculosis is intrinsically tolerant to many antibiotics largely due to the imperviousness of its unusual mycolic acid-containing cell wall to most antimicrobials. The emergence and increasingly widespread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) revitalized keen interest in phage-inspired therapy. SWU1gp39 is a novel gene from mycobacteriophage SWU1 with unknown function. SWU1gp39 expressed in M. smegmatis conferred the host cell increased susceptibility to multiple antibiotics, including isoniazid, erythromycin, norfloxacin, ampicillin, ciprofloxacin, ofloxacin, rifampicin and vancomycin, and multiple environment stresses such as H2O2, heat shock, low pH and SDS...
2016: Scientific Reports
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