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Tuberculosis AND cholesterol

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https://www.readbyqxmd.com/read/28515464/systems-immunology-of-diabetes-tuberculosis-comorbidity-reveals-signatures-of-disease-complications
#1
Cesar A Prada-Medina, Kiyoshi F Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flávio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A Menon, Vijay Viswanathan, Bruno B Andrade, Helder I Nakaya, Hardy Kornfeld
Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479115/statin-use-is-associated-with-a-lower-risk-of-tuberculosis
#2
Vincent Yi-Fong Su, Wei-Juin Su, Yung-Feng Yen, Sheng-Wei Pan, Pei-Hung Chuang, Jia-Yih Feng, Kun-Ta Chou, Kuang-Yao Yang, Yu-Chin Lee, Tzeng-Ji Chen
BACKGROUND: Statins are widely used to lower cholesterol levels and cardiovascular risk. Further, studies have shown that statins may decrease the risks of infectious diseases and infection-related mortality. However, the association between statin use and active tuberculosis (TB) disease remains unclear. METHODS: Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. Patients taking statins during 2000-2013, without antecedent TB disease, were included...
May 4, 2017: Chest
https://www.readbyqxmd.com/read/28464471/chemical-activation-of-adenylyl-cyclase-rv1625c-inhibits-growth-of-mycobacterium-tuberculosis-on-cholesterol-and-modulates-intramacrophage-signaling
#3
Richard M Johnson, Guangchun Bai, Christopher M DeMott, Nilesh K Banavali, Christine R Montague, Caroline Moon, Alexander Shekhtman, Brian VanderVen, Kathleen A McDonough
Mycobacterium tuberculosis (Mtb) uses a complex 3', 5'-cyclic AMP (cAMP) signaling network to sense and respond to changing environments encountered during infection, so perturbation of cAMP signaling might be leveraged to disrupt Mtb pathogenesis. However, understanding of cAMP signaling pathways is hindered by the presence of at least 15 distinct adenylyl cyclases (ACs). Recently, the small molecule V-58 was shown to inhibit Mtb replication within macrophages and stimulate cAMP production in Mtb. Here we determined that V-58 rapidly and directly activates Mtb AC Rv1625c to produce high levels of cAMP regardless of the bacterial environment or growth medium...
May 2, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28461265/preparation-and-characterization-of-isoniazid-loaded-crude-soybean-lecithin-liposomes
#4
Christian Isalomboto Nkanga, Rui Werner Krause, Xavier Siwe Noundou, Roderick Bryan Walker
Tuberculosis (TB) is a poverty related infectious disease that is rapidly giving rise to public health concerns. Lengthy drug administration and frequent adverse side-effects associated with TB treatment make anti-tubercular drugs (ATDs) good candidates for drug delivery studies. This work aimed to formulate and prepare liposomes as a cost-effective option for ATD delivery. Liposomes were prepared by film hydration using crude soybean lecithin (CL) and not pure phospholipids as in the normal practice. Cholesterol was also used (up to 25% mass ratio), and isoniazid (INH) was encapsulated as model drug using a freeze-thaw loading technique...
April 29, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28447386/unravelling-the-pleiotropic-role-of-the-mceg-atpase-in-mycobacterium-smegmatis
#5
Julia García-Fernández, Kadamba Papavinasasundaram, Beatriz Galán, Christopher M Sassetti, José L García
The Mce systems are complex ABC transporters that are encoded by different numbers of homologous operons in Actinobacteria. While the four Mce systems of Mycobacterium tuberculosis are all energized by a single ATPase, MceG, each system appears to import different fatty acids or sterols. To explore if this behaviour can be extended to saprophytic mycobacteria, whose more complex genomes encode more Mce systems, we have identified and characterized the MceG orthologue of Mycobacterium smegmatis. This bacterium relies on MceG to energize its six Mce systems that contribute to a variety of cellular functions including sterol uptake and cell envelope maintenance...
April 26, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28419200/switching-to-efavirenz-versus-remaining-on-ritonavir-boosted-lopinavir-in-hiv-infected-children-exposed-to-nevirapine-long-term-outcomes-of-a-randomized-trial
#6
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 non-inferiority of switching to efavirenz (EFV) versus remaining on ritonavir-boosted lopinavir (LPV/r) for virologic control in HIV-infected children exposed to nevirapine (NVP) for prevention of mother-to-child transmission. Here we assess outcomes up to four 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...
April 17, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28380256/investigation-of-the-mycobacterial-enzyme-hsad-as-a-potential-novel-target-for-anti-tubercular-agents-using-a-fragment-based-drug-design-approach
#7
Ali Ryan, Elena Polycarpou, Nathan A Lack, Dimitrios Evangelopoulos, Christian Sieg, Alice Halman, Sanjib Bhakta, Olga Eleftheriadou, Timothy D McHugh, Sebastian Keany, Edward D Lowe, Romain Ballet, Areej Abuhammad, William R Jacobs, Alessio Ciulli, Edith Sim
BACKGROUND AND PURPOSE: With the emergence of extensively drug-resistant tuberculosis, there is a need for new anti-tubercular drugs that work through novel mechanisms of action. The meta cleavage product hydrolase, HsaD, has been demonstrated to be critical for the survival of Mycobacterium tuberculosis in macrophages and is encoded in an operon involved in cholesterol catabolism, which is identical in M. tuberculosis and M. bovis BCG. EXPERIMENTAL APPROACH: We generated a mutant strain of M...
April 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28377529/catabolism-of-the-last-two-steroid-rings-in-mycobacterium-tuberculosis-and-other-bacteria
#8
Adam M Crowe, Israël Casabon, Kirstin L Brown, Jie Liu, Jennifer Lian, Jason C Rogalski, Timothy E Hurst, Victor Snieckus, Leonard J Foster, Lindsay D Eltis
Most mycolic acid-containing actinobacteria and some proteobacteria use steroids as growth substrates, but the catabolism of the last two steroid rings has yet to be elucidated. In Mycobacterium tuberculosis, this pathway includes virulence determinants and has been proposed to be encoded by the KstR2-regulated genes, which include a predicted coenzyme A (CoA) transferase gene (ipdAB) and an acyl-CoA reductase gene (ipdC). In the presence of cholesterol, ΔipdC and ΔipdAB mutants of either M. tuberculosis or Rhodococcus jostii strain RHA1 accumulated previously undescribed metabolites: 3aα-H-4α(carboxyl-CoA)-5-hydroxy-7aβ-methylhexahydro-1-indanone (5-OH HIC-CoA) and (R)-2-(2-carboxyethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA (COCHEA-CoA), respectively...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28364349/effect-of-blood-biochemical-factors-on-nontraumatic-necrosis-of-the-femoral-head-logistic-regression-analysis
#9
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/28335738/genome-wide-expression-profiling-establishes-novel-modulatory-roles-of-vitamin-c-in-thp-1-human-monocytic-cell-line
#10
Sakshi Dhingra Batra, Malobi Nandi, Kriti Sikri, Jaya Sivaswami Tyagi
BACKGROUND: Vitamin C (vit C) is an essential dietary nutrient, which is a potent antioxidant, a free radical scavenger and functions as a cofactor in many enzymatic reactions. Vit C is also considered to enhance the immune effector function of macrophages, which are regarded to be the first line of defence in response to any pathogen. The THP-1 cell line is widely used for studying macrophage functions and for analyzing host cell-pathogen interactions. RESULTS: We performed a genome-wide temporal gene expression and functional enrichment analysis of THP-1 cells treated with 100 μM of vit C, a physiologically relevant concentration of the vitamin...
March 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28250431/novel-protein-acetyltransferase-rv2170-modulates-carbon-and-energy-metabolism-in-mycobacterium-tuberculosis
#11
Wonsik Lee, Brian C VanderVen, Suzanne Walker, David G Russell
Recent data indicate that the metabolism of Mycobacterium tuberculosis (Mtb) inside its host cell is heavily dependent on cholesterol and fatty acids. Mtb exhibits a unique capacity to co-metabolize different carbon sources and the products from these substrates are compartmentalized metabolically. Isocitrate lies at one of the key nodes of carbon metabolism and can feed into either the glyoxylate shunt (via isocitrate lyase) or the TCA cycle (via isocitrate dehydrogenase (ICDH) activity) and we sought to better understand the regulation at this junction...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28237027/cholesterol-plays-a-larger-role-during-mycobacterium-tuberculosis-in%C3%A2-vitro-dormancy-and-reactivation-than-previously-suspected
#12
Maria D Soto-Ramirez, Diana A Aguilar-Ayala, Lazaro Garcia-Morales, Sofia M Rodriguez-Peredo, Claudia Badillo-Lopez, Diana E Rios-Muñiz, Mario A Meza-Segura, Gelen Y Rivera-Morales, Lizbel Leon-Solis, Jorge F Cerna-Cortes, Sandra Rivera-Gutierrez, Addy C Helguera-Repetto, Jorge A Gonzalez-Y-Merchand
It is known that cholesterol plays a key role for Mycobacterium tuberculosis (Mtb) adaptation and survival within the host, thus contributing to the establishment of dormancy. It has been extensively demonstrated that fatty acids are the main energy source of Mtb during infection and dormancy, and it has been proposed that these molecules are implicated in reactivation of bacilli from a dormant state. We used in vitro models to analyze Mtb gene expression during dormancy and reactivation when fatty acids and cholesterol are the unique carbon source in the media...
March 2017: Tuberculosis
https://www.readbyqxmd.com/read/28228760/perturbed-microrna-expression-by-mycobacterium-tuberculosis-promotes-macrophage-polarization-leading-to-pro-survival-foam-cell
#13
Pankaj Kumar Ahluwalia, Rajan Kumar Pandey, Prabodh Kumar Sehajpal, Vijay Kumar Prajapati
Tuberculosis (TB) is one of the prevalent causes of death worldwide, with 95% of these deaths occurring in developing countries, like India. The causative agent, Mycobacterium tuberculosis (MTb) has the tenacious ability to circumvent the host's immune system for its own advantage. Macrophages are one of the phagocytic cells that are central to immunity against MTb. These are highly plastic cells dependent on the milieu and can showcase M1/M2 polarization. M1 macrophages are bactericidal in action, but M2 macrophages are anti-inflammatory in their immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28217856/molecular-characterization-of-a-new-gene-cluster-for-steroid-degradation-in-mycobacterium-smegmatis
#14
Lorena Fernández-Cabezón, Esther García-Fernández, Beatriz Galán, José L García
The C-19 steroids 4-androstene-3,17-dione (AD), 1,4-androstadiene-3,17-dione (ADD) or 9α-hydroxy-4-androstene-3,17-dione (9OH-AD), which have been postulated as intermediates of the cholesterol catabolic pathway in Mycobacterium smegmatis, cannot be used as sole carbon and energy sources by this bacterium. Only the ΔkstR mutant which constitutively expresses the genes repressed by the KstR regulator can metabolize AD and ADD with severe difficulties but still cannot metabolize 9OH-AD, suggesting that these compounds are not true intermediates but side products of the cholesterol pathway...
February 20, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28193630/mycolates-of-mycobacterium-tuberculosis-modulate-the-flow-of-cholesterol-for-bacillary-proliferation-in-murine-macrophages
#15
Ilke Vermeulen, Mark Baird, Juma Al-Dulayymi, Muriel Smet, Jan Verschoor, Johan Grooten
The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of Mycobacterium tuberculosis (Mtb), can induce this foam phenotype possibly as a way to perturb host cell lipid homeostasis to support the infection. It is not exactly clear how MAs allow differentiation of foam cells during Mtb infection. Here we investigated how chemically synthetic MAs, each with a defined stereochemistry similar to natural Mtb-associated mycolates, influence cell foamy phenotype and mycobacterial proliferation in murine host macrophages...
April 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28043638/activity-of-drugs-against-dormant-mycobacterium-tuberculosis
#16
A Iacobino, G Piccaro, F Giannoni, A Mustazzolu, L Fattorini
OBJECTIVE/BACKGROUND: Heterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (TB) patients, with Mycobacterium tuberculosis (Mtb) existing from actively replicating (AR) to dormant, nonreplicating (NR) stages. Within cellular granulomas, the pH is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the pH varies between 7.2 and 7.4. To combat TB, we should kill both AR and NR stages of Mtb...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28002883/cholesterol-metabolism-a-potential-therapeutic-target-in-mycobacteria
#17
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/27943261/efavirenz-or-nevirapine-in-three-drug-combination-therapy-with-two-nucleoside-or-nucleotide-reverse-transcriptase-inhibitors-for-initial-treatment-of-hiv-infection-in-antiretroviral-na%C3%A3-ve-individuals
#18
REVIEW
Lawrence Mbuagbaw, Sara Mursleen, James H Irlam, Alicen B Spaulding, George W Rutherford, Nandi Siegfried
BACKGROUND: The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP)...
December 10, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27879023/potential-effect-of-ezetimibe-against-mycobacterium-tuberculosis-infection-in-type-ii-diabetes
#19
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...
April 2017: 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
#20
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
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