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https://read.qxmd.com/read/30743161/identification-of-glucosyl-3-phosphoglycerate-phosphatase-as-a-novel-drug-target-against-resistant-strain-of-mycobacterium-tuberculosis-xdr1219-by-using-comparative-metabolic-pathway-approach
#1
Reaz Uddin, Noor-Ul-Ain Zahra, Syed Sikander Azam
Tuberculosis (TB) is a major global health challenge. It has been afflicting human for thousands of years and is still severely affecting a huge population. The etiological agent of the disease is Mycobacterium tuberculosis (MTB) that survives in the human host in latent, dormant, and non-replicative state by evading the immune system. It is one of the leading causes of infection related death worldwide. The situation is exacerbated by the massive increase in the resistant strains such as multi-drug resistant TB (MDR-TB) and extensive drug-resistant TB (XDR-TB)...
January 24, 2019: Computational Biology and Chemistry
https://read.qxmd.com/read/30740456/the-extracellular-matrix-of-mycobacterial-biofilms-could-we-shorten-the-treatment-of-mycobacterial-infections
#2
REVIEW
Poushali Chakraborty, Ashwani Kumar
A number of non-tuberculous mycobacterium species are opportunistic pathogens and ubiquitously form biofilms. These infections are often recalcitrant to treatment and require therapy with multiple drugs for long duration. The biofilm resident bacteria also display phenotypic drug tolerance and thus it has been hypothesized that the drug unresponsiveness in vivo could be due to formation of biofilms inside the host. We have discussed the biofilms of several pathogenic non-tuberculous mycobacterium (NTM) species in context to the in vivo pathologies...
January 18, 2019: Microbial Cell
https://read.qxmd.com/read/30737374/corticosteroids-inhibit-mycobacterium-tuberculosis-induced-necrotic-host-cell-death-by-abrogating-mitochondrial-membrane-permeability-transition
#3
Jessica Gräb, Isabelle Suárez, Edeltraud van Gumpel, Sandra Winter, Fynn Schreiber, Anna Esser, Christoph Hölscher, Melanie Fritsch, Marc Herb, Michael Schramm, Laurens Wachsmuth, Christian Pallasch, Manolis Pasparakis, Hamid Kashkar, Jan Rybniker
Corticosteroids are host-directed drugs with proven beneficial effect on survival of tuberculosis (TB) patients, but their precise mechanisms of action in this disease remain largely unknown. Here we show that corticosteroids such as dexamethasone inhibit necrotic cell death of cells infected with Mycobacterium tuberculosis (Mtb) by facilitating mitogen-activated protein kinase phosphatase 1 (MKP-1)-dependent dephosphorylation of p38 MAPK. Characterization of infected mixed lineage kinase domain-like (MLKL) and tumor necrosis factor receptor 1 (TNFR1) knockout cells show that the underlying mechanism is independent from TNFα-signaling and necroptosis...
February 8, 2019: Nature Communications
https://read.qxmd.com/read/30717477/different-signaling-pathways-define-different-interferon-stimulated-gene-expression-during-mycobacteria-infection-in-macrophages
#4
Xinying Zhou, Jiahui Yang, Zelin Zhang, Lijie Zhang, Bo Zhu, Linmiao Lie, Yubin Huang, Rui Ma, Chaoying Zhou, Shengfeng Hu, Qian Wen, Li Ma
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated genes (ISGs) in human macrophages (Mϕs) remains unknown. In this study, we investigated the expression-signature and associated innate signaling mechanisms of ISGs in Mtb-infected human monocyte-derived Mϕs (hMDMs) and THP-1-derived Mϕs (THP-1-Mϕs)...
February 3, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30713272/introducing-broadened-antibacterial-activity-to-rhodanine-derivatives-targeting-enoyl-acyl-carrier-protein-reductase
#5
Zhi-Gang Sun, Yun-Jie Xu, Jian-Fei Xu, Qi-Xing Liu, Yu-Shun Yang, Hai-Liang Zhu
Broadened antibacterial activity was introduced to rhodanine derivatives targeting Mycobacterial tuberculosis enoyl-acyl carrier protein reductase (Mtb InhA) by recruiting feature of xacins to bring DNA Gyrase B inhibitory capability. This is significant for preventing further bacterial injections in the tuberculosis treatment. The most potent compound Cy14 suggested comparable bioactivity (IC50  = 3.18 µM for Mtb InhA; IC50  = 10 nM for DNA Gyrase B) with positive controls. Structure-activity relationship discussion and molecular docking model revealed the significance of rhodanine moiety and derived methoxyl on meta-position, pointing out orientations for future modification...
2019: Chemical & Pharmaceutical Bulletin
https://read.qxmd.com/read/30711546/mycobacterium-tuberculosis-ag85b-hfc%C3%AE-1-recombinant-fusion-protein-as-a-selective-receptor-dependent-delivery-system-for-antigen-presentation
#6
Mohsen Karbalaei Zadeh Babaki, Mahboubeh Taghiabadi, Saman Soleimanpour, Masoud Saleh Moghadam, Arman Mosavat, Abbas Ali Amini, Mohammad Ali Mohammadi, Seyed Abdolrahim Rezaee
Introducing an effective vaccine for tuberculosis (TB) is an urgent need. Mycobacterium tuberculosis (Mtb) Ag85 complex is suggested for making protective immunodominant antigens for design and development of novel TB vaccine. In the present study, a pDR2EF1-Fcγ1 vector has been used to make Ag85B:hFcγ1 recombinant fusion protein. Briefly, specific XbaI and NotI site incorporated primers were used to amplify Mtb-fbpB gene by PCR, TA-cloned and amplified in E.coli DH5α. The resulting vector then subcloned into the pDR2EF1...
January 31, 2019: Microbial Pathogenesis
https://read.qxmd.com/read/30710621/expression-of-glyceraldehyde-3-phosphate-dehydrogenase-from-m-tuberculosis-in-e-coli-purification-and-characteristics-of-the-untagged-recombinant-enzyme
#7
E V Schmalhausen, M S Shumkov, V I Muronetz, V K Švedas
The goal of the present work was to produce glyceraldehyde-3-phospate dehydrogenase from M. tuberculosis in E. coli cells in soluble and catalytically active form and to elaborate a method for the purification of the recombinant enzyme. The His-tagged recombinant enzyme (Mtb-GAPDH_His) was shown to be inactive and insoluble. The untagged enzyme (Mtb-GAPDH) was catalytically active and exhibited higher solubility. Mtb-GAPDH was purified from the cell extract using ammonium sulfate fractionation and ion-exchange chromatography...
January 30, 2019: Protein Expression and Purification
https://read.qxmd.com/read/30705156/opposing-reactions-in-coenzyme-a-metabolism-sensitize-mycobacterium-tuberculosis-to-enzyme-inhibition
#8
Elaine Ballinger, John Mosior, Travis Hartman, Kristin Burns-Huang, Ben Gold, Roxanne Morris, Laurent Goullieux, Isabelle Blanc, Julien Vaubourgeix, Sophie Lagrange, Laurent Fraisse, Stéphanie Sans, Cedric Couturier, Eric Bacqué, Kyu Rhee, Sarah M Scarry, Jeffrey Aubé, Guangbin Yang, Ouathek Ouerfelli, Dirk Schnappinger, Thomas R Ioerger, Curtis A Engelhart, Jennifer A McConnell, Kathrine McAulay, Allison Fay, Christine Roubert, James Sacchettini, Carl Nathan
Mycobacterium tuberculosis (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb's cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4'-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction...
February 1, 2019: Science
https://read.qxmd.com/read/30695094/disruption-of-intestinal-homeostasis-and-intestinal-microbiota-during-experimental-autoimmune-uveitis
#9
Cathleen Janowitz, Yukiko K Nakamura, Christina Metea, Abigail Gligor, William Yu, Lisa Karstens, James T Rosenbaum, Mark Asquith, Phoebe Lin
Purpose: We determine the changes in intestinal microbiota and/or disruptions in intestinal homeostasis during uveitis. Methods: Experimental autoimmune uveitis (EAU) was induced in B10.RIII mice with coadministration of interphotoreceptor retinoid-binding protein peptide (IRBP) and killed mycobacterial antigen (MTB) as an adjuvant. Using 16S rRNA gene sequencing, we looked at intestinal microbial differences during the course of uveitis, as well as intestinal morphologic changes, changes in intestinal permeability by FITC-dextran leakage, antimicrobial peptide expression in the gastrointstinal tract, and T lymphocyte prevalence before and at peak intraocular inflammation...
January 2, 2019: Investigative Ophthalmology & Visual Science
https://read.qxmd.com/read/30691253/oxidized-carbon-nanosphere-based-subunit-vaccine-delivery-system-elicited-robust-th1-and-cytotoxic-t-cell-responses
#10
Pritsana Sawutdeechaikul, Felipe Cia, Gregory J Bancroft, Supason Wanichwecharungruang, Chutamath Sittplangkoon, Tanapat Palaga
Subunit vaccine is safe and more stable than live vaccine but it has disadvantage in eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanosphere (OCN) was used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCN to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) were investigated...
January 29, 2019: Journal of Microbiology and Biotechnology
https://read.qxmd.com/read/30689080/optimisation-of-human-v-h-domain-antibodies-specific-to-mycobacterium-tuberculosis-heat-shock-protein-hsp16-3
#11
Jia Xin Soong, Soo Khim Chan, Theam Soon Lim, Yee Siew Choong
Mycobacterium tuberculosis (Mtb) 16.3 kDa heat shock protein 16.3 (HSP16.3) is a latency-associated antigen that can be targeted for latent tuberculosis (TB) diagnostic and therapeutic development. We have previously developed human VH domain antibodies (dAbs; clone E3 and F1) specific against HSP16.3. In this work, we applied computational methods to optimise and design the antibodies in order to improve the binding affinity with HSP16.3. The VH domain antibodies were first docked to the dimer form of HSP16...
January 28, 2019: Journal of Computer-aided Molecular Design
https://read.qxmd.com/read/30680034/lectins-of-mycobacterium-tuberculosis-rarely-studied-proteins
#12
REVIEW
Katharina Kolbe, Sri Kumar Veleti, Norbert Reiling, Thisbe K Lindhorst
The importance of bacterial lectins for adhesion, pathogenicity, and biofilm formation is well established for many Gram-positive and Gram-negative bacteria. However, there is very little information available about lectins of the tuberculosis-causing bacterium, Mycobacterium tuberculosis ( Mtb ). In this paper we review previous studies on the carbohydrate-binding characteristics of mycobacteria and related Mtb proteins, discussing their potential relevance to Mtb infection and pathogenesis.
2019: Beilstein Journal of Organic Chemistry
https://read.qxmd.com/read/30663302/quantitative-lipid-droplet-proteomics-reveals-mycobacterium-tuberculosis-induced-alterations-in-macrophage-response-to-infection
#13
Dilip Menon, Kaurab Singh, Sneha M Pinto, Ananya Nandy, Neetika Jaisinghani, Rintu Kutum, Debasis Dash, Ts Keshava Prasad, Sheetal Gandotra
Growing evidence suggests the importance of lipid metabolism in pathogenesis of tuberculosis. Neutral lipids form the majority of lipids in a caseous granuloma, pathology characteristic of tuberculosis. Cytosolic lipid droplets (LDs) of macrophages form the store house of these lipids, and have been demonstrated to contribute to the inflammatory response to infection. The proteome of lipid droplets reflects the mechanisms of lipid metabolism active under a condition. However, infection induced changes in the proteome of these dynamic organelles remains elusive...
January 21, 2019: ACS Infectious Diseases
https://read.qxmd.com/read/30660186/recombinant-o-mannosylated-protein-production-psts-1-from-mycobacterium-tuberculosis-in-pichia-pastoris-komagataella-phaffii-as-a-tool-to-study-tuberculosis-infection
#14
Giroshi Bando-Campos, Daniel Juárez-López, Sergio A Román-González, Antonia I Castillo-Rodal, Clarita Olvera, Yolanda López-Vidal, Roberto Arreguín-Espinosa, Clara Espitia, Mauricio A Trujillo-Roldán, Norma A Valdez-Cruz
BACKGROUND: Pichia pastoris (syn. Komagataella phaffii) is one of the most highly utilized eukaryotic expression systems for the production of heterologous glycoproteins, being able to perform both N- and O-mannosylation. In this study, we present the expression in P. pastoris of an O-mannosylated recombinant version of the 38 kDa glycolipoprotein PstS-1 from Mycobacterium tuberculosis (Mtb), that is similar in primary structure to the native secreted protein. RESULTS: The recombinant PstS-1 (rPstS-1) was produced without the native lipidation signal...
January 19, 2019: Microbial Cell Factories
https://read.qxmd.com/read/30651075/pleural-ifn-%C3%AE-release-assay-combined-with-biomarkers-distinguished-effectively-tuberculosis-from-malignant-pleural-effusion
#15
Yimin Tang, Juanjuan Zhang, Huarong Huang, Xing He, Jiaohong Zhang, Min Ou, Guobao Li, Changchun Zeng, Taosheng Ye, Lili Ren, Yingxia Liu, Guoliang Zhang
BACKGROUND: Tuberculosis (TB) remains a major public health concern on a global scale, especially in developing nations. So far, no formal guidelines are available for the diagnosis and treatment of tuberculosis pleurisy. The diagnosis of TB is worsened by the immense difficulty in differential determination of tuberculosis pleural effusion (TPE) and malignant pleural effusion (MPE). The purpose of this investigation is to assess the differential diagnostic efficiencies of the pleural IFN-γ release assay (IGRA) and widely-used biochemical parameters in the distinction analysis of TPE and MPE...
January 16, 2019: BMC Infectious Diseases
https://read.qxmd.com/read/30641319/docking-and-pharmacophore-based-virtual-screening-for-the-identification-of-novel-mycobacterium-tuberculosis-protein-tyrosine-phosphatase-b-mptpb-inhibitor-with-a-thiobarbiturate-scaffold
#16
Dongfeng Zhang, Yun Lin, Xi Chen, Wenting Zhao, Dongni Chen, Meng Gao, Qinglin Wang, Bin Wang, Haihong Huang, Yongjun Lu, Yu Lu
Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (MptpB) is an important virulence factor for Mtb that contributes to survival of the bacteria in macrophages. The absence of a human ortholog makes MptpB an attractive target for new therapeutics to treat tuberculosis. MptpB inhibitors could be an effective treatment to overcome emerging TB drug resistance. Adopting a structure-based virtual screening strategy, we successfully identified thiobarbiturate-based drug-like MptpB inhibitor 15 with an IC50 of 22...
December 31, 2018: Bioorganic Chemistry
https://read.qxmd.com/read/30633392/physical-and-functional-interaction-between-nucleoid-associated-proteins-hu-and-lsr2-of-mycobacterium-tuberculosis-altered-dna-binding-and-gene-regulation
#17
Chandreyee Datta, Rajiv Kumar Jha, Wareed Ahmed, Sohini Ganguly, Soumitra Ghosh, Valakunja Nagaraja
Nucleoid-associated proteins (NAPs) in bacteria contribute to key activities such as DNA compaction, chromosome organization, and regulation of gene expression. HU and Lsr2 are two principal NAPs in Mycobacterium tuberculosis (Mtb). HU is essential for Mtb survival and is one of the most abundant NAPs. It differs from other eubacterial HU proteins in having a long, flexible lysine- and arginine-rich carboxy-terminal domain. Lsr2 of Mtb is the functional analogue of the bacterial NAP commonly called H-NS. Lsr2 binds to and regulates expression of A/T-rich portions of the otherwise G/C-rich mycobacterial chromosome...
January 11, 2019: Molecular Microbiology
https://read.qxmd.com/read/30615070/biophysical-characterization-and-ligand-binding-properties-of-the-elongation-factor-tu-from-mycobacterium-tuberculosis
#18
Juanjuan Yang, Jing Hong, Ling Luo, Ke Liu, Chun Meng, Zhi-Liang Ji, Donghai Lin
Mycobacterium tuberculosis (Mtb) is the key devastating bacterial pathogen responsible for tuberculosis. Increasing emergence of multi-drug-resistant, extensively drug-resistant, and rifampicin/isoniazid-resistant strains of Mtb makes the discovery of validated drug targets an urgent priority. As a vital translational component of the protein biosynthesis system, elongation factor Tu (EF-Tu) is an important molecular switch responsible for selection and binding of the cognate aminoacyl-tRNA to the acceptor site on the ribosome...
January 7, 2019: Acta Biochimica et Biophysica Sinica
https://read.qxmd.com/read/30602415/2-3d-qsar-molecular-docking-and-md-simulation-studies-of-ftsz-protein-targeting-benzimidazoles-derivatives
#19
Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Neeraj Dwivedi, Md Imtaiyaz Hassan
The development of multi-drug and extensively-drug resistant strains of Mycobacterium tuberculosis (Mtb) have encouraged to develop new anti-TB agents with a unique mechanism of action. FtsZ, an essential protein of bacterial cytokinesis, has emerged as a validated target for antibacterial therapy. This study describes the utility of benzimidazoles (BI) derivatives as potential FtsZ inhibitors. Through 2/3D QSAR (MLR) molecular modeling, new BI-inhibitors with improved activity have been designed. Statistically significant models from 2D-QSAR (r2  = 0...
December 27, 2018: Computational Biology and Chemistry
https://read.qxmd.com/read/30581260/comparative-proteomic-profiling-of-mycobacterium-tuberculosis-and-the-thai-vaccine-strain-mycobacterium-bovis-bacille-calmette-guerin-tokyo172-diverse-biomarker-candidates-for-species-differentiation
#20
Songsri Kasempimolporn, Pornpimol Premchaiporn, Wichit Thaveekarn, Supatsorn Boonchang, Visith Sitprija
Background: Bacille Calmette-Guerin (BCG)-related complications can occur in vaccinated children. Comparison of the composition of cellular proteins of virulent Mycobacterium tuberculosis (MTB) H37Rv with of attenuated Mycobacterium bovis BCG Tokyo172 vaccine strain used in Thailand and identify protein candidates of value for differentiation between the two mycobacterial species may facilitate the diagnosis of etiologic agent of mycobacterial disease in vaccinated children, as most cases have been believed to have originated from BCG vaccine...
October 2018: Journal of Global Infectious Diseases
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