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Lipid metabolism tuberculosis

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https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#1
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28522365/knowns-and-unknowns-of-membrane-lipid-synthesis-in-streptomycetes
#2
Mario Sandoval-Calderón, Ziqiang Guan, Christian Sohlenkamp
Bacteria belonging to the genus Streptomyces are among the most prolific producers of antibiotics. Research on cellular membrane biosynthesis and turnover is lagging behind in Streptomyces compared to related organisms like Mycobacterium tuberculosis. While natural products discovery in Streptomyces is evidently a priority in order to discover new antibiotics to combat the increase in antibiotic resistant pathogens, a better understanding of this cellular compartment should provide insights into the interplay between core and secondary metabolism...
May 15, 2017: Biochimie
https://www.readbyqxmd.com/read/28475832/a-phenotypic-based-target-screening-approach-delivers-new-antitubercular-ctp-synthetase-inhibitors
#3
Marta Esposito, Sára Szadocka, Giulia Degiacomi, Beatrice S Orena, Giorgia Mori, Valentina Piano, Francesca Boldrin, Júlia Zemanová, Stanislav Huszár, David Barros, Sean Ekins, Joel Lelièvre, Riccardo Manganelli, Andrea Mattevi, Maria Rosalia Pasca, Giovanna Riccardi, Lluis Ballell, Katarína Mikušová, Laurent R Chiarelli
Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds...
May 11, 2017: ACS Infectious Diseases
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
#4
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/28412202/the-immunosuppressive-effects-of-a-novel-recombinant-lipq-rv2485c-protein-of-mycobacterium-tuberculosis-on-human-macrophage-cell-lines
#5
Anjani Kumar, Manisha, Gurkamaljit Kaur Sangha, Anju Shrivastava, Jagdeep Kaur
Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28364349/effect-of-blood-biochemical-factors-on-nontraumatic-necrosis-of-the-femoral-head-logistic-regression-analysis
#6
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/28338924/a-nonsynonymous-snp-catalog-of-mycobacterium-tuberculosis-virulence-genes-and-its-use-for-detecting-new-potentially-virulent-sublineages
#7
Natalya E Mikheecheva, Marina V Zaychikova, Alexander V Melerzanov, Valery N Danilenko
Mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an M. tuberculosis classification approach based on functional polymorphisms in virulence genes. An M. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin-antitoxin systems...
April 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28337966/acid-fast-positive-and-acid-fast-negative-mycobacterium-tuberculosis-the-koch-paradox
#8
Catherine Vilchèze, Laurent Kremer
Acid-fast (AF) staining, also known as Ziehl-Neelsen stain microscopic detection, developed over a century ago, is even today the most widely used diagnostic method for tuberculosis. Herein we present a short historical review of the evolution of AF staining methods and discuss Koch's paradox, in which non-AF tubercle bacilli can be detected in tuberculosis patients or in experimentally infected animals. The conversion of Mycobacterium tuberculosis from an actively growing, AF-positive form to a nonreplicating, AF-negative form during the course of infection is now well documented...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28327797/bacterial-immunostat-mycobacterium-tuberculosis-lipids-and-their-role-in-the-host-immune-response
#9
REVIEW
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
#10
Gurkamaljit Kaur, Varinder Saini, Bandana Kumari, Jasbinder Kaur, 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
#11
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
#12
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
#13
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
#14
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
#15
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...
December 1, 2016: 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
#16
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
#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/27936614/structural-basis-for-the-strict-substrate-selectivity-of-the-mycobacterial-hydrolase-lipw
#18
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
#19
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
#20
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
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