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Tuberculosis AND cholesterol

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https://www.readbyqxmd.com/read/27879023/potential-effect-of-ezetimibe-against-mycobacterium-tuberculosis-infection-in-type-ii-diabetes
#1
I-Fang Tsai, Chiu-Ping Kuo, Andrew B Lin, Ming-Nan Chien, Hsin-Tsung Ho, Tsai-Yin Wei, Chien-Liang Wu, Yen-Ta Lu
BACKGROUND AND OBJECTIVE: Tuberculosis (TB) risk might be increased in patients with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host lipids are essential energy sources used by mycobacteria to persist in a latent TB state. A potential therapy targeting cholesterol catabolism of mycobacteria has been proposed, but the potential of cholesterol-lowering drugs as anti-TB therapy is unclear. The purpose of this study was to determine the effects of ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular mycobacteria survival and dormancy...
November 23, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27867565/changes-in-cholesterol-level-correlate-with-the-course-of-pulmonary-nontuberculous-mycobacterial-disease
#2
Ji Young Hong, Go Eun Yang, Yousang Ko, Yong Bum Park, Yun Su Sim, Sung Hoon Park, Chang Youl Lee, Ki-Suck Jung, Myung Goo Lee
BACKGROUND: Nutritional assessment is important in patients with pulmonary nontuberculous mycobacterial (PNTM) disease. The therapeutic effect of a cholesterol-rich diet in tuberculosis (TB) patients has been demonstrated, but the role of cholesterol in PNTM disease is unclear. This study evaluated the sequential changes in nutritional markers, including cholesterol, total lymphocyte count and visceral fat volume, according to the PNTM disease course. METHODS: This was an age-, sex- and number of comorbid diseases-matched case-control analysis of 89 patients with PNTM disease and 356 controls, who were participants in a Korean national survey...
October 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27856345/drug-targeting-of-heme-proteins-in-mycobacterium-tuberculosis
#3
REVIEW
Kirsty J McLean, Andrew W Munro
TB, caused by the human pathogen Mycobacterium tuberculosis (Mtb, causes more deaths than any other infectious disease. Iron is crucial for Mtb to infect the host and to sustain infection, with Mtb encoding large numbers of iron-binding proteins. Many of these are hemoproteins with key roles, including defense against oxidative stress, cellular signaling and regulation, host cholesterol metabolism, and respiratory processes. Various heme enzymes in Mtb are validated drug targets and/or products of genes essential for bacterial viability or survival in the host...
November 14, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27847019/expression-profile-of-mce4-operon-of-mycobacterium-tuberculosis-following-environmental-stress
#4
Nisha Rathor, Kushal Garima, Naresh Kumar Sharma, Anshika Narang, Mandira Varma-Basil, Mridula Bose
BACKGROUND: The mce4 operon is one of the four mce operons with eight genes (yrbE4A, yrbE4B, mce4A, mce4B, mce4C, mce4D, mce4E and mce4F) of Mycobacterium tuberculosis. It expresses in the later phase of infection and imports cholesterol for long term survival of the bacilli. To cause latent infection, M. tuberculosis undergoes metabolic reprogramming of its genes to survive in the hostile environment like low availability of oxygen and nutrition depletion inside the host. OBJECTIVE: To analyze real time expression profile of mce4 operon under various stress conditions...
September 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27804278/mycobacterium-smegmatis-is-a-suitable-cell-factory-for-the-production-of-steroidic-synthons
#5
Beatriz Galán, Iria Uhía, Esther García-Fernández, Igor Martínez, Esther Bahíllo, Juan L de la Fuente, José L Barredo, Lorena Fernández-Cabezón, José L García
A number of pharmaceutical steroid synthons are currently produced through the microbial side-chain cleavage of natural sterols as an alternative to multi-step chemical synthesis. Industrially, these synthons have been usually produced through fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc(2) 155 is a model organism for tuberculosis studies which uses cholesterol as the sole carbon and energy source for growth, as other mycobacterial strains...
November 2, 2016: Microbial Biotechnology
https://www.readbyqxmd.com/read/27771519/-genetic-regulation-of-mycobacterium-tuberculosis-in-a-lipid-rich-environment
#6
REVIEW
Diana A Aguilar-Ayala, Juan Carlos Palomino, Peter Vandamme, Anandi Martin, Jorge A Gonzalez-Y-Merchand
Tuberculosis (TB) remains as one of the leading causes of morbidity and mortality among infectious diseases worldwide. Although lipids (mainly fatty acids and cholesterol) have been reported to play an important role during active and latent infection of M. tuberculosis, there are other molecular aspects of bacterial response to those substrates that are not fully understood, involving gene regulation background. This review highlights recent insights on pathogen gene expression: regulation during its active growth, during survival in presence of lipids and under variable hostile host microenvironments...
October 19, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27751911/prxq-b-from-mycobacterium-tuberculosis-is-a-monomeric-thioredoxin-dependent-and-highly-efficient-fatty-acid-hydroperoxide-reductase
#7
Aníbal M Reyes, Diego S Vazquez, Ari Zeida, Martín Hugo, M Dolores Piñeyro, María Inés De Armas, Darío Estrin, Rafael Radi, Javier Santos, Madia Trujillo
Mycobacterium tuberculosis (M. tuberculosis) is the intracellular bacterium responsible for tuberculosis disease (TD). Inside the phagosomes of activated macrophages, M. tuberculosis is exposed to cytotoxic hydroperoxides such as hydrogen peroxide, fatty acid hydroperoxides and peroxynitrite. Thus, the characterization of the bacterial antioxidant systems could facilitate novel drug developments. In this work, we characterized the product of the gene Rv1608c from M. tuberculosis, which according to sequence homology had been annotated as a putative peroxiredoxin of the peroxiredoxin Q subfamily (PrxQ B from M...
October 15, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27718364/uptake-and-metabolism-of-fluorescent-steroids-by-mycobacterial-cells
#8
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...
October 5, 2016: Steroids
https://www.readbyqxmd.com/read/27677638/discovery-and-biophysical-evaluation-of-first-low-nanomolar-hits-targeting-cyp125-of-m-%C3%A2-tuberculosis
#9
Christian Brengel, Andreas Thomann, Alexander Schifrin, Jens Eberhard, Rolf W Hartmann
Tuberculosis, which is predominantly caused by Mycobacterium tuberculosis (Mtb), is still the most lethal bacterial infection with 1.5 million casualties in 2014. Moreover, the fact that the appearance of resistant mutants and long-term treatment are coupled with economic problems in developing countries hampers an efficient therapy. Interference with the essential cholesterol metabolism of Mtb could be a promising novel strategy to fight Mtb infections. CYP125, a P450 enzyme in Mtb, has been shown to play an important role in this metabolic pathway...
September 28, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27672155/inhibiting-mycobacterium-tuberculosis-within-and-without
#10
REVIEW
Stewart T Cole
Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials...
November 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27632901/topical-simvastatin-as-host-directed-therapy-against-severity-of-cutaneous-leishmaniasis-in-mice
#11
Suraj P Parihar, Mary-Anne Hartley, Ramona Hurdayal, Reto Guler, Frank Brombacher
We recently demonstrated that statins mediate protection against intracellular pathogens, Mycobacterium tuberculosis and Listeria monocytogenes in mice. Here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by Leishmania major (LV39). In an ear infection model, topical application of simvastatin directly on established lesions significantly reduced severity of the disease reflected by ear lesion size and ulceration...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27621864/characteristics-of-patients-with-pseudochylothorax-a-systematic-review
#12
Adriana Lama, Lucía Ferreiro, María E Toubes, Antonio Golpe, Francisco Gude, José M Álvarez-Dobaño, Francisco J González-Barcala, Esther San José, Nuria Rodríguez-Núñez, Carlos Rábade, Carlota Rodríguez-García, Luis Valdés
BACKGROUND: Pseudochylothorax (PCT) (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion (PE) that is commonly associated with chronic inflammatory disorders. Nevertheless, the characteristics of patients with PCT are poorly defined. METHODS: A systematic review was performed across two electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of PCT. Case descriptions and retrospective studies were included...
August 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27604870/alu-repeats-as-transcriptional-regulatory-platforms-in-macrophage-responses-to-m-tuberculosis-infection
#13
Manuella Bouttier, David Laperriere, Babak Memari, Joseph Mangiapane, Amanda Fiore, Eric Mitchell, Mark Verway, Marcel A Behr, Robert Sladek, Luis B Barreiro, Sylvie Mader, John H White
To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo H3K4me1 peaks in infected cells were associated with genes implicated in host defenses and apoptosis. Our analysis revealed that 40% of de novo regions contained human/primate-specific Alu transposable elements, enriched in the AluJ and S subtypes. These contained several transcription factor binding sites, including those for members of the MEF2 and ATF families, and LXR and RAR nuclear receptors, all of which have been implicated in macrophage differentiation, survival, and responses to stress and infection...
September 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27587433/necrotic-cell-sensor-clec4e-promotes-a-proatherogenic-macrophage-phenotype-through-activation-of-the-unfolded-protein-response
#14
Marc Clément, Gemma Basatemur, Leanne Masters, Lauren Baker, Patrick Bruneval, Takao Iwawaki, Manfred Kneilling, Sho Yamasaki, Jane Goodall, Ziad Mallat
BACKGROUND: Atherosclerotic lesion expansion is characterized by the development of a lipid-rich necrotic core known to be associated with the occurrence of complications. Abnormal lipid handling, inflammation, and alteration of cell survival or proliferation contribute to necrotic core formation, but the molecular mechanisms involved in this process are not properly understood. C-type lectin receptor 4e (Clec4e) recognizes the cord factor of Mycobacterium tuberculosis but also senses molecular patterns released by necrotic cells and drives inflammation...
October 4, 2016: Circulation
https://www.readbyqxmd.com/read/27559961/prevalence-and-risk-factors-for-efavirenz-based-antiretroviral-treatment-associated-severe-vitamin-d-deficiency-a-prospective-cohort-study
#15
Hanna Nylén, Abiy Habtewold, Eyasu Makonnen, Getnet Yimer, Leif Bertilsson, Jürgen Burhenne, Ulf Diczfalusy, Eleni Aklillu
Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD.Treatment-naïve Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27492019/potential-of-surface-eroding-poly-ethylene-carbonate-for-drug-delivery-to-macrophages
#16
Adam Bohr, Jorrit J Water, Yingya Wang, Lærke Arnfast, Moritz Beck-Broichsitter
Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the tuberculosis drug rifampicin to study the characteristics and performance of PEC as a potential carrier for controlled drug delivery to macrophages. All drug-loaded PLGA and PEC films were amorphous indicating good miscibility of the drug in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more rapidly and near-linearly via enzyme mediated surface erosion (by cholesterol esterase)...
September 25, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27355757/purification-and-structural-characterization-of-mce4a-from-mycobacterium-tuberculosis
#17
Shagufta Khan, Asimul Islam, Md Imtaiyaz Hassan, Faizan Ahmad
The mce4A gene of Mycobacterium tuberculosis encodes a 400 amino acid residues protein of 43kDa, which is a mammalian cell entry protein (Mce4A) and plays important role in host cell invasion. Mce4A helps in long-term survival of M. tuberculosis by cholesterol utilization. Host cholesterol utilization mechanism by Mce4A is not clearly understood. In order to investigate the role of Mce4A in M. tuberculosis pathogenesis, we purified the recombinant protein by affinity chromatography, analyzed by SDS-PAGE and confirmed by western blot...
June 26, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27279584/therapeutic-efficacy-of-nigella-sativa-linn-against-antituberculosis-drug-induced-hepatic-injury-in-wistar-rats
#18
Amita Jaswal, Monika Sharma, Suchita Raghuvanshi, Samta Sharma, Mohd Salim Reshi, Chhavi Uthra, Sangeeta Shukla
Antituberculosis drug (ATD)-induced hepatotoxicity is a major impediment for the effective treatment of tuberculosis (TB). All first-line anti-TB medications have adverse effects that interrupt the successful completion of TB treatment. This investigation focuses on the evaluation of the protective role of Nigella sativa (NS) against liver injury caused by ATDs. Female rats were treated with ATDs for 8 weeks (3 d/wk) followed by NS for 8 weeks (3 d/wk). The antioxidant activity of NS was estimated with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and by analyzing total phenolic contents...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27196901/in-vitro-activity-of-copper-ii-complexes-loaded-or-unloaded-into-a-nanostructured-lipid-system-against-mycobacterium-tuberculosis
#19
Patricia B da Silva, Paula C de Souza, Giovana Maria Fioramonti Calixto, Erica de O Lopes, Regina C G Frem, Adelino V G Netto, Antonio E Mauro, Fernando R Pavan, Marlus Chorilli
Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin(®) HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl₂(INH)₂]·H₂O (1), [Cu(NCS)₂(INH)₂]·5H₂O (2) and [Cu(NCO)₂(INH)₂]·4H₂O (3)...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27164097/genome-wide-transcriptome-profiling-of-mycobacterium-smegmatis-mc%C3%A2-155-cultivated-in-minimal-media-supplemented-with-cholesterol-androstenedione-or-glycerol
#20
Qun Li, Fanglan Ge, Yunya Tan, Guangxiang Zhang, Wei Li
Mycobacterium smegmatis strain MC² 155 is an attractive model organism for the study of M. tuberculosis and other mycobacterial pathogens, as it can grow well using cholesterol as a carbon resource. However, its global transcriptomic response remains largely unrevealed. In this study, M. smegmatis MC² 155 cultivated in androstenedione, cholesterol and glycerol supplemented media were collected separately for a RNA-Sequencing study. The results showed that 6004, 6681 and 6348 genes were expressed in androstenedione, cholesterol and glycerol supplemented media, and 5891 genes were expressed in all three conditions, with 237 specially expressed in cholesterol added medium...
2016: International Journal of Molecular Sciences
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