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Lipid metabolism tuberculosis

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https://www.readbyqxmd.com/read/28062754/mycobacterium-tuberculosis-complex-exhibits-lineage-specific-variations-affecting-protein-ductility-and-epitope-recognition
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27325376/the-perilipin-like-ppe15-protein-in-mycobacterium-tuberculosis-is-required-for-triacylglycerol-accumulation-under-dormancy-inducing-conditions
#15
Jaiyanth Daniel, Nidhi Kapoor, Tatiana Sirakova, Rajesh Sinha, Pappachan Kolattukudy
Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one-third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin-1 and was upregulated in Mtb dormancy. We generated a ppe15 gene-disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three-dimensional human granuloma model...
September 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27268593/new-insights-into-the-mycolate-containing-compound-biosynthesis-and-transport-in-mycobacteria
#16
REVIEW
Annaïk Quémard
Mycolic acids are extremely-long-chain fatty acids that compose a large family of mycolate-containing compounds, major envelope lipid components and critical pathogenicity factors of Mycobacterium tuberculosis. In recent years there have been major advances in understanding their metabolic pathway. Unknown enzymes of the fatty acid synthase type II elongation system and the condensation system that builds the mycolic acid scaffold were identified. Missing links with the mycolate-containing compound biosynthesis-such as the mechanisms of transfer onto trehalose and of translocation through the inner membrane-were deciphered, while recycling processes have emerged...
September 2016: Trends in Microbiology
https://www.readbyqxmd.com/read/27247233/targeting-mycobacterium-tuberculosis-tumor-necrosis-factor-alpha-downregulating-genes-for-the-development-of-antituberculous-vaccines
#17
Aaron Olsen, Yong Chen, Qingzhou Ji, Guofeng Zhu, Aruna Dharshan De Silva, Catherine Vilchèze, Torin Weisbrod, Weimin Li, Jiayong Xu, Michelle Larsen, Jinghang Zhang, Steven A Porcelli, William R Jacobs, John Chan
UNLABELLED: Tumor necrosis factor alpha (TNF) plays a critical role in the control of Mycobacterium tuberculosis, in part by augmenting T cell responses through promoting macrophage phagolysosomal fusion (thereby optimizing CD4(+) T cell immunity by enhancing antigen presentation) and apoptosis (a process that can lead to cross-priming of CD8(+) T cells). M. tuberculosis can evade antituberculosis (anti-TB) immunity by inhibiting host cell TNF production via expression of specific mycobacterial components...
May 31, 2016: MBio
https://www.readbyqxmd.com/read/27233038/the-fbpase-encoding-gene-glpx-is-required-for-gluconeogenesis-bacterial-proliferation-and-division-in-vivo-of-mycobacterium-marinum
#18
Jingfeng Tong, Lu Meng, Xinwei Wang, Lixia Liu, Liangdong Lyu, Chuan Wang, Yang Li, Qian Gao, Chen Yang, Chen Niu
Lipids have been identified as important carbon sources for Mycobacterium tuberculosis (Mtb) to utilize in vivo. Thus gluconeogenesis bears a key role for Mtb to survive and replicate in host. A rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (FBPase) is encoded by the gene glpX. The functions of glpX were studied in M. marinum, a closely related species to Mtb. The glpX deletion strain (ΔglpX) displayed altered gluconeogenesis, attenuated virulence, and altered bacterial proliferation...
2016: PloS One
https://www.readbyqxmd.com/read/27231718/cell-envelope-remodeling-as-a-determinant-of-phenotypic-antibacterial-tolerance-in-mycobacterium-tuberculosis
#19
Gérald Larrouy-Maumus, Leonardo B Marino, Ashoka V R Madduri, T J Ragan, Debbie M Hunt, Lucrezia Bassano, Maximiliano G Gutierrez, D Branch Moody, Fernando R Pavan, Luiz Pedro S de Carvalho
The mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. We investigate whether changes in NaCl concentration toward physiologically higher values affect antibacterial efficacy against Mycobacterium tuberculosis (Mtb), the causal agent of human tuberculosis. Indeed, multiclass phenotypic antibacterial tolerance is observed during Mtb growth in physiologic saline. This includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several aminoglycosides, and quinolones...
May 13, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27227307/the-role-of-biotin-in-bacterial-physiology-and-virulence-a-novel-antibiotic-target-for-mycobacterium-tuberculosis
#20
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
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