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Journal articles on the topic 'Mycobacterial Protein Synthesis'

Author: Grafiati

Published: 4 June 2021

Last updated: 6 September 2023

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1

Gan, Wei Chong, Hien Fuh Ng, and Yun Fong Ngeow. "Mechanisms of Linezolid Resistance in Mycobacteria." Pharmaceuticals 16, no. 6 (2023): 784. http://dx.doi.org/10.3390/ph16060784.

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Mycobacteria form some of the most notorious and difficult-to-treat bacterial pathogens. As a group, they are intrinsically resistant to many commonly used antibiotics, such as tetracyclines and beta-lactams. In addition to intrinsic resistances, acquired multidrug resistance has also been observed and documented in Mycobacterium tuberculosis (MTB), Mycobacterium leprae and non-tuberculous mycobacteria (NTM). To combat multidrug resistant infections by these pathogens, innovative antimicrobials and treatment regimens are required. In this regard, linezolid, an oxazolidinone introduced for clin

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2

Rao, Alka, Geeta Ram, Adesh Kumar Saini, et al. "Synthesis and Selection of De Novo Proteins That Bind and Impede Cellular Functions of an Essential Mycobacterial Protein." Applied and Environmental Microbiology 73, no. 4 (2006): 1320–31. http://dx.doi.org/10.1128/aem.02461-06.

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ABSTRACT Recent advances in nonrational and part-rational approaches to de novo peptide/protein design have shown increasing potential for development of novel peptides and proteins of therapeutic use. We demonstrated earlier the usefulness of one such approach recently developed by us, called “codon shuffling,” in creating stand-alone de novo protein libraries from which bioactive proteins could be isolated. Here, we report the synthesis and selection of codon-shuffled de novo proteins that bind to a selected Mycobacterium tuberculosis protein target, the histone-like protein HupB, believed t

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Doherty, T. M., R. J. Booth, S. G. Love, J. J. Gibson, D. R. Harding, and J. D. Watson. "Characterization of an antibody-binding epitope from the 18-kDa protein on Mycobacterium leprae." Journal of Immunology 142, no. 5 (1989): 1691–95. http://dx.doi.org/10.4049/jimmunol.142.5.1691.

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Abstract A murine mAb, designated L5, appears to be specific for an epitope on a protein from Mycobacterium leprae of restricted distribution within the mycobacteria. This protein, of Mr 18,000 (18 kDa) is of interest because monoclonal antibodies raised against it do not appear to cross-react with other mycobacterial pathogens. The L5 antibody-binding epitope has been mapped by two complementary methods; expression of gene fragments and synthesis of short peptides. This L5-binding region of the 18-kDa protein (amino acids 109 to 115) shows some homology to a region of the GroEL heat shock fam

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Rodrigues, José, Vanessa T. Almeida, Ana L. Rosário, et al. "High Throughput Expression Screening of Arabinofuranosyltransferases from Mycobacteria." Processes 9, no. 4 (2021): 629. http://dx.doi.org/10.3390/pr9040629.

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Studies on membrane proteins can help to develop new drug targets and treatments for a variety of diseases. However, membrane proteins continue to be among the most challenging targets in structural biology. This uphill endeavor can be even harder for membrane proteins from Mycobacterium species, which are notoriously difficult to express in heterologous systems. Arabinofuranosyltransferases are involved in mycobacterial cell wall synthesis and thus potential targets for antituberculosis drugs. A set of 96 mycobacterial genes coding for Arabinofuranosyltransferases was selected, of which 17 we

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Driss, Virginie, Fanny Legrand, Emmanuel Hermann та ін. "TLR2-dependent eosinophil interactions with mycobacteria: role of α-defensins". Blood 113, № 14 (2009): 3235–44. http://dx.doi.org/10.1182/blood-2008-07-166595.

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AbstractPeripheral blood and tissue eosinophilia are a prominent feature in allergic diseases and during helminth infections. Eosinophil recruitment also frequently occurs upon mycobacterial infections, particularly in lung granuloma. However, the mechanism by which eosinophils interact with mycobacteria remains largely unknown. Because eosinophils recently have been shown to be involved in innate immune responses, we investigated the direct interactions of eosinophils with Mycobacterium bovis BCG as a study model. We show that live BCG attracts human eosinophils and induces reactive oxygen sp

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Roach, Shannon K., and Jeffrey S. Schorey. "Differential Regulation of the Mitogen-Activated Protein Kinases by Pathogenic and Nonpathogenic Mycobacteria." Infection and Immunity 70, no. 6 (2002): 3040–52. http://dx.doi.org/10.1128/iai.70.6.3040-3052.2002.

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ABSTRACT Mycobacteria are the etiologic agents of numerous diseases which account for significant morbidity and mortality in humans and other animal species. Many mycobacteria are intramacrophage pathogens and therefore the macrophage response to infection, which includes synthesis of cytokines such as tumor necrosis factor alpha (TNF-α) and production of nitric oxide, has important consequences for host immunity. However, very little is known about the macrophage cell signaling pathways initiated upon infection or how pathogenic mycobacteria may modulate the macrophage responses. Using primar

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Mir, Mushtaq, Sladjana Prisic, Choong-Min Kang, et al. "Mycobacterial GenecuvAIs Required for Optimal Nutrient Utilization and Virulence." Infection and Immunity 82, no. 10 (2014): 4104–17. http://dx.doi.org/10.1128/iai.02207-14.

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ABSTRACTTo persist and cause disease in the host,Mycobacterium tuberculosismust adapt to its environment during infection. Adaptations include changes in nutrient utilization and alterations in growth rate.M. tuberculosisRv1422 is a conserved gene of unknown function that was found in a genetic screen to interact with themce4cholesterol uptake locus. The Rv1422 protein is phosphorylated by theM. tuberculosisSer/Thr kinases PknA and PknB, which regulate cell growth and cell wall synthesis.Bacillus subtilisstrains lacking the Rv1422 homologueyvcKgrow poorly on several carbon sources, andyvcKis r

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Gupta, Kuldeepkumar Ramnaresh, Gunjan Arora, Abid Mattoo, and Andaleeb Sajid. "Stringent Response in Mycobacteria: From Biology to Therapeutic Potential." Pathogens 10, no. 11 (2021): 1417. http://dx.doi.org/10.3390/pathogens10111417.

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Mycobacterium tuberculosis is a human pathogen that can thrive inside the host immune cells for several years and cause tuberculosis. This is due to the propensity of M. tuberculosis to synthesize a sturdy cell wall, shift metabolism and growth, secrete virulence factors to manipulate host immunity, and exhibit stringent response. These attributes help M. tuberculosis to manage the host response, and successfully establish and maintain an infection even under nutrient-deprived stress conditions for years. In this review, we will discuss the importance of mycobacterial stringent response under

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9

Gobala Krishnan P, Gnanaprakash K, and Chandrasekhar KB. "Design, synthesis, characterization and antitubercular activity of some nov-el 2, 4-disubstituted thiazole derivatives." International Journal of Research in Pharmaceutical Sciences 10, no. 2 (2019): 1504–9. http://dx.doi.org/10.26452/ijrps.v10i2.729.

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Literature reviews reveal that thiazole and pyrazine carboxamide derivatives exhibit anticonvulsant, antimicrobial, anticancer and anti-tubercular activities due to the presence of –S-C=N- and-CO–NH- moiety. A series of thiazolyl pyrazine carboxamide derivatives (5a-j) were synthesized by condensation reaction between 2-amino, 4-substituted phenyl 2-amino thiazole and pyrazine 2-carboxylic acid. These synthesized thiazole derivatives (5a-j) were evaluated for their inhibitory activity against Mycobacterium tuberculosis (Mtb), H37Rv using microplate Alamar Blue assay (MABA). The compound, 5c an

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Katsube, Tomoya, Sohkichi Matsumoto, Masaki Takatsuka, et al. "Control of Cell Wall Assembly by a Histone-Like Protein in Mycobacteria." Journal of Bacteriology 189, no. 22 (2007): 8241–49. http://dx.doi.org/10.1128/jb.00550-07.

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ABSTRACT Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been el

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Greve, Jennifer, Axel Mogk, and Uli Kazmaier. "Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives." Marine Drugs 20, no. 10 (2022): 632. http://dx.doi.org/10.3390/md20100632.

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Ilamycins/rufomycins are marine cycloheptapeptides containing unusual amino acids. Produced by Streptomyces sp., these compounds show potent activity against a range of mycobacteria, including multidrug-resistant strains of Mycobacterium tuberculosis. The cyclic peptides target the AAA+ protein ClpC1 that, together with the peptidases ClpP1/ClpP2, forms an essential ATP-driven protease. Derivatives of the ilamycins with a simplified tryptophane unit are synthesized in a straightforward manner. The ilamycin derivative 26 with a cyclic hemiaminal structure is active in the nM-range against sever

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Hu, Zhe, and John E. Cronan. "The primary step of biotin synthesis in mycobacteria." Proceedings of the National Academy of Sciences 117, no. 38 (2020): 23794–801. http://dx.doi.org/10.1073/pnas.2010189117.

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Biotin plays an essential role in growth of mycobacteria. Synthesis of the cofactor is essential forMycobacterium tuberculosisto establish and maintain chronic infections in a murine model of tuberculosis. Although the late steps of mycobacterial biotin synthesis, assembly of the heterocyclic rings, are thought to follow the canonical pathway, the mechanism of synthesis of the pimelic acid moiety that contributes most of the biotin carbon atoms is unknown. We report that theMycobacterium smegmatisgene annotated as encoding Tam, anO-methyltransferase that monomethylates and detoxifiestrans-acon

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Brzostek, Anna, Filip Gąsior, Jakub Lach, et al. "ATP-Dependent Ligases and AEP Primases Affect the Profile and Frequency of Mutations in Mycobacteria under Oxidative Stress." Genes 12, no. 4 (2021): 547. http://dx.doi.org/10.3390/genes12040547.

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The mycobacterial nonhomologous end-joining pathway (NHEJ) involved in double-strand break (DSB) repair consists of the multifunctional ATP-dependent ligase LigD and the DNA bridging protein Ku. The other ATP-dependent ligases LigC and AEP-primase PrimC are considered as backup in this process. The engagement of LigD, LigC, and PrimC in the base excision repair (BER) process in mycobacteria has also been postulated. Here, we evaluated the sensitivity of Mycolicibacterium smegmatis mutants defective in the synthesis of Ku, Ku-LigD, and LigC1-LigC2-PrimC, as well as mutants deprived of all these

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Ezquerra-Aznárez, José Manuel, Giulia Degiacomi, Henrich Gašparovič, et al. "The Veterinary Anti-Parasitic Selamectin Is a Novel Inhibitor of the Mycobacterium tuberculosis DprE1 Enzyme." International Journal of Molecular Sciences 23, no. 2 (2022): 771. http://dx.doi.org/10.3390/ijms23020771.

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Avermectins are macrocyclic lactones with anthelmintic activity. Recently, they were found to be effective against Mycobacterium tuberculosis, which accounts for one third of the worldwide deaths from antimicrobial resistance. However, their anti-mycobacterial mode of action remains to be elucidated. The activity of selamectin was determined against a panel of M. tuberculosis mutants. Two strains carrying mutations in DprE1, the decaprenylphosphoryl-β-D-ribose oxidase involved in the synthesis of mycobacterial arabinogalactan, were more susceptible to selamectin. Biochemical assays against the

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Kuron, Aneta, Malgorzata Korycka-Machala, Anna Brzostek, et al. "Evaluation of DNA Primase DnaG as a Potential Target for Antibiotics." Antimicrobial Agents and Chemotherapy 58, no. 3 (2013): 1699–706. http://dx.doi.org/10.1128/aac.01721-13.

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ABSTRACTMycobacteria contain genes for several DNA-dependent RNA primases, includingdnaG, which encodes an essential replication enzyme that has been proposed as a target for antituberculosis compounds. Anin silicoanalysis revealed that mycobacteria also possess archaeo-eukaryotic superfamily primases (AEPs) of unknown function. Using a homologous recombination system, we obtained direct evidence that wild-typednaGcannot be deleted from the chromosome ofMycobacterium smegmatiswithout disrupting viability, even in backgrounds in which mycobacterial AEPs are overexpressed. In contrast, single-de

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Sinha, Sudhir, K. Kosalai, Shalini Arora, et al. "Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics." Microbiology 151, no. 7 (2005): 2411–19. http://dx.doi.org/10.1099/mic.0.27799-0.

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Membrane-associated proteins of Mycobacterium tuberculosis offer a challenge, as well as an opportunity, in the quest for better therapeutic and prophylactic interventions against tuberculosis. The authors have previously reported that extraction with the detergent Triton X-114 (TX-114) is a useful step in proteomic analysis of mycobacterial cell membranes, and detergent-soluble membrane proteins of mycobacteria are potent stimulators of human T cells. In this study 1-D and 2-D gel electrophoresis-based protocols were used for the analysis of proteins in the TX-114 extract of M. tuberculosis m

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17

Patel, Onisha, Rajini Brammananth, Weiwen Dai, et al. "Crystal structure of the putative cell-wall lipoglycan biosynthesis protein LmcA from Mycobacterium smegmatis." Acta Crystallographica Section D Structural Biology 78, no. 4 (2022): 494–508. http://dx.doi.org/10.1107/s2059798322001772.

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The bacterial genus Mycobacterium includes important pathogens, most notably M. tuberculosis, which infects one-quarter of the entire human population, resulting in around 1.4 million deaths from tuberculosis each year. Mycobacteria, and the closely related corynebacteria, synthesize a class of abundant glycolipids, the phosphatidyl-myo-inositol mannosides (PIMs). PIMs serve as membrane anchors for hyperglycosylated species, lipomannan (LM) and lipoarabinomannan (LAM), which are surface-exposed and modulate the host immune response. Previously, in studies using the model species Corynebacteriu

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18

Suttmann, Henrik, Nadine Lehan, Andreas Böhle, and Sven Brandau. "Stimulation of Neutrophil Granulocytes with Mycobacterium bovis Bacillus Calmette-Guérin Induces Changes in Phenotype and Gene Expression and Inhibits Spontaneous Apoptosis." Infection and Immunity 71, no. 8 (2003): 4647–56. http://dx.doi.org/10.1128/iai.71.8.4647-4656.2003.

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ABSTRACT Polymorphonuclear neutrophil granulocytes (PMN) have been implicated in the early inflammatory response against mycobacteria besides monocytes/macrophages. Yet, little is known about the interaction of mycobacteria with PMN. We investigated the potential of Mycobacterium bovis bacillus Calmette-Guérin (BCG) to stimulate and influence PMN phenotype, gene expression profile and spontaneous apoptosis. Flow cytometric analyses revealed an upregulation of the function-associated molecules Fcγ receptor III (FcγR III) and II (CD16 and CD32) as well as MAC-1 (CD11b and CD18) on BCG-stimulate

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19

Berman, J. S., R. L. Blumenthal, H. Kornfeld, et al. "Chemotactic activity of mycobacterial lipoarabinomannans for human blood T lymphocytes in vitro." Journal of Immunology 156, no. 10 (1996): 3828–35. http://dx.doi.org/10.4049/jimmunol.156.10.3828.

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Abstract A crucial early event in tuberculosis is the ingestion of Mycobacterium tuberculosis (Mtb) by alveolar macrophages. Chemotactic factors released by infected macrophages are likely to initiate a granulomatous response, a key feature of host resistance to tuberculosis. To date, the role of mycobacterial products in regulating the granulomatous response has not been clearly defined. Here we report that the mycobacterial cell wall glycophospholipid lipoarabinomannan (LAM) could specifically induce human peripheral blood T cell chemotaxis in vitro. Both terminally mannosylated LAM isolated

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Ghosh, Shreya, Sourabh Samaddar, Prithwiraj Kirtania, and Sujoy K. Das Gupta. "A DinB Ortholog Enables Mycobacterial Growth under dTTP-Limiting Conditions Induced by the Expression of a Mycobacteriophage-Derived Ribonucleotide Reductase Gene." Journal of Bacteriology 198, no. 2 (2015): 352–62. http://dx.doi.org/10.1128/jb.00669-15.

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ABSTRACTMycobacteriumspecies such asM. smegmatisandM. tuberculosisencode at least two translesion synthesis (TLS) polymerases, DinB1 and DinB2, respectively. Although predicted to be linked to DNA repair, their rolein vivoremains enigmatic.M. smegmatismc2155, a strain commonly used to investigate mycobacterial genetics, has two copies ofdinB2, the gene that codes for DinB2, by virtue of a 56-kb chromosomal duplication. Expression of a mycobacteriophage D29 gene (gene 50) encoding a class II ribonucleotide reductase inM. smegmatisΔDRKIN, a strain derived from mc2155 in which one copy of the dup

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Stinear, Timothy P., Melinda J. Pryor, Jessica L. Porter, and Stewart T. Cole. "Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans." Microbiology 151, no. 3 (2005): 683–92. http://dx.doi.org/10.1099/mic.0.27674-0.

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The presence of a 174 kb plasmid called pMUM001 in Mycobacterium ulcerans, the first example of a mycobacterial plasmid encoding a virulence determinant, was recently reported. Over half of pMUM001 is devoted to six genes, three of which encode giant polyketide synthases (PKS) that produce mycolactone, an unusual cytotoxic lipid produced by M. ulcerans. In this present study the remaining 75 non-PKS-associated protein-coding sequences (CDS) are analysed and it is shown that pMUM001 is a low-copy-number element with a functional ori that supports replication in Mycobacterium marinum but not in

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Slayden, R. A., R. E. Lee, J. W. Armour, et al. "Antimycobacterial action of thiolactomycin: an inhibitor of fatty acid and mycolic acid synthesis." Antimicrobial Agents and Chemotherapy 40, no. 12 (1996): 2813–19. http://dx.doi.org/10.1128/aac.40.12.2813.

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Thiolactomycin (TLM) possesses in vivo antimycobacterial activity against the saprophytic strain Mycobacterium smegmatis mc2155 and the virulent strain M. tuberculosis Erdman, resulting in complete inhibition of growth on solid media at 75 and 25 micrograms/ml, respectively. Use of an in vitro murine macrophage model also demonstrated the killing of viable intracellular M. tuberculosis in a dose-dependent manner. Through the use of in vivo [1,2-14C]acetate labeling of M. smegmatis, TLM was shown to inhibit the synthesis of both fatty acids and mycolic acids. However, synthesis of the shorter-c

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Rodriguez, G. Marcela, Martin I. Voskuil, Benjamin Gold, Gary K. Schoolnik, and Issar Smith. "ideR, an Essential Gene in Mycobacterium tuberculosis: Role of IdeR in Iron-Dependent Gene Expression, Iron Metabolism, and Oxidative Stress Response." Infection and Immunity 70, no. 7 (2002): 3371–81. http://dx.doi.org/10.1128/iai.70.7.3371-3381.2002.

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ABSTRACT The mycobacterial IdeR protein is a metal-dependent regulator of the DtxR (diphtheria toxin repressor) family. In the presence of iron, it binds to a specific DNA sequence in the promoter regions of the genes that it regulates, thus controlling their transcription. In this study, we provide evidence that ideR is an essential gene in Mycobacterium tuberculosis. ideR cannot normally be disrupted in this mycobacterium in the absence of a second functional copy of the gene. However, a rare ideR mutant was obtained in which the lethal effects of ideR inactivation were alleviated by a secon

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Thomas, Sherine E., Andrew J. Whitehouse, Karen Brown, et al. "Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification." Nucleic Acids Research 48, no. 14 (2020): 8099–112. http://dx.doi.org/10.1093/nar/gkaa539.

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Abstract Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. F

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Yamazaki, Yoshitaka, Lia Danelishvili, Martin Wu, Molly MacNab, and Luiz E. Bermudez. "Mycobacterium avium Genes Associated with the Ability To Form a Biofilm." Applied and Environmental Microbiology 72, no. 1 (2006): 819–25. http://dx.doi.org/10.1128/aem.72.1.819-825.2006.

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ABSTRACT Mycobacterium avium is widely distributed in the environment, and it is chiefly found in water and soil. M. avium, as well as Mycobacterium smegmatis, has been recognized to produce a biofilm or biofilm-like structure. We screened an M. avium green fluorescent protein (GFP) promoter library in M. smegmatis for genes involved in biofilm formation on polyvinyl chloride (PVC) plates. Clones associated with increased GFP expression ≥2.0-fold over the baseline were sequenced. Seventeen genes, most encoding proteins of the tricarboxylic acid (TCA) cycle and GDP-mannose and fatty acid biosyn

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Danelishvili, Lia, Martin Wu, Lowell S. Young, and Luiz E. Bermudez. "Genomic Approach to Identifying the Putative Target of and Mechanisms of Resistance to Mefloquine in Mycobacteria." Antimicrobial Agents and Chemotherapy 49, no. 9 (2005): 3707–14. http://dx.doi.org/10.1128/aac.49.9.3707-3714.2005.

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ABSTRACT The emergence of mycobacterial resistance to multiple antimicrobials emphasizes the need for new compounds. The antimycobacterial activity of mefloquine has been recently described. Mycobacterium avium, Mycobacterium smegmatis, and Mycobacterium tuberculosis are susceptible to mefloquine in vitro, and activity was evidenced in vivo against M. avium. Attempts to obtain resistant mutants by both in vitro and in vivo selection have failed. To identify mycobacterial genes regulated in response to mefloquine, we employed DNA microarray and green fluorescent protein (GFP) promoter library t

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Malik, Muhammad, Tao Lu, Xilin Zhao, et al. "Lethality of Quinolones against Mycobacterium smegmatis in the Presence or Absence of Chloramphenicol." Antimicrobial Agents and Chemotherapy 49, no. 5 (2005): 2008–14. http://dx.doi.org/10.1128/aac.49.5.2008-2014.2005.

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ABSTRACT Quinolones were examined for rapid lethal activity against Mycobacterium smegmatis in the presence and absence of chloramphenicol, an inhibitor of protein synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents enhanced rapid killing. With the surprising exception of moxifloxacin, higher quinolone concentrations were required for lethal activity in the presence of chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone dimers, which represent quinolones with large

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Gurvitz, Aner, J. Kalervo Hiltunen, and Alexander J. Kastaniotis. "Heterologous Expression of Mycobacterial Proteins in Saccharomyces cerevisiae Reveals Two Physiologically Functional 3-Hydroxyacyl-Thioester Dehydratases, HtdX and HtdY, in Addition to HadABC and HtdZ." Journal of Bacteriology 191, no. 8 (2009): 2683–90. http://dx.doi.org/10.1128/jb.01046-08.

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ABSTRACT We report on Mycobacterium tuberculosis Rv0241c and Rv3389c, representing two physiologically functional 3-hydroxyacyl-thioester dehydratases (Htd). These enzymes are potentially entrained in type 2 fatty acid synthase (FASII). Mycobacterial FASII is involved in the synthesis of mycolic acids, which are the major constituents of the protective layer around the pathogen, shielding it from noxious chemicals and the host's immune system. Mycolic acids are additionally associated with the virulence and resilience of M. tuberculosis. Here, Rv0241c and Rv3389c, which are distinct from the p

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Lewthwaite, Jo C., Anthony R. M. Coates, Peter Tormay, et al. "Mycobacterium tuberculosisChaperonin 60.1 Is a More Potent Cytokine Stimulator than Chaperonin 60.2 (Hsp 65) and Contains a CD14-Binding Domain." Infection and Immunity 69, no. 12 (2001): 7349–55. http://dx.doi.org/10.1128/iai.69.12.7349-7355.2001.

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ABSTRACT Much attention has focused on the Mycobacterium tuberculosis molecular chaperone chaperonin (Cpn) 60.2 (Hsp 65) in the pathology of tuberculosis because of its immunogenicity and ability to directly activate human monocytes and vascular endothelial cells. However, M. tuberculosis is one of a small group of bacteria that contain multiple genes encoding Cpn 60 proteins. We have now cloned and expressed both M.tuberculosis proteins and report that the novel chaperonin 60, Cpn 60.1, is a more potent inducer of cytokine synthesis than is Cpn 60.2. This is in spite of 76% amino acid sequenc

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Sarathy, Jickky Palmae, Gerhard Gruber, and Thomas Dick. "Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline." Antibiotics 8, no. 4 (2019): 261. http://dx.doi.org/10.3390/antibiotics8040261.

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Bedaquiline (BDQ) inhibits ATP generation in Mycobacterium tuberculosis by interfering with the F-ATP synthase activity. Two mechanisms of action of BDQ are broadly accepted. A direct mechanism involves BDQ binding to the enzyme’s c-ring to block its rotation, thus inhibiting ATP synthesis in the enzyme’s catalytic α3β3-headpiece. An indirect mechanism involves BDQ uncoupling electron transport in the electron transport chain from ATP synthesis at the F-ATP synthase. In a recently uncovered second direct mechanism, BDQ binds to the enzyme’s ε-subunit to disrupt its ability to link c-ring rotat

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Mikušová, Katarína, Martina Beláňová, Jana Korduláková, et al. "Identification of a Novel Galactosyl Transferase Involved in Biosynthesis of the Mycobacterial Cell Wall." Journal of Bacteriology 188, no. 18 (2006): 6592–98. http://dx.doi.org/10.1128/jb.00489-06.

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ABSTRACT The possibility of the Rv3782 protein of Mycobacterium tuberculosis being a putative galactosyl transferase (GalTr) implicated in galactan synthesis arose from its similarity to the known GalTr Rv3808c, its classification as a nucleotide sugar-requiring inverting glycosyltransferase (GT-2 family), and its location within the “possible arabinogalactan biosynthetic gene cluster” of M. tuberculosis. In order to study the function of the enzyme, active membrane and cell wall fractions from Mycobacterium smegmatis containing the overexpressed Rv3782 protein were incubated with endogenous d

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Matsunaga, Isamu, Apoorva Bhatt, David C. Young, et al. "Mycobacterium tuberculosis pks12 Produces a Novel Polyketide Presented by CD1c to T Cells." Journal of Experimental Medicine 200, no. 12 (2004): 1559–69. http://dx.doi.org/10.1084/jem.20041429.

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CD1c-mediated T cells are activated by a mycobacterial phospholipid antigen whose carbohydrate structure precisely corresponds to mammalian mannosyl β-1-phosphodolichol (MPD), but contains an unusual lipid moiety. Here, we show that this T cell antigen is a member of a family of branched, alkane lipids that vary in length (C30-34) and are produced by medically important mycobacteria such as M. tuberculosis and M. bovis Bacille-Calmette-Guerin. The alkane moiety distinguished these mycobacterial lipid antigens from mammalian MPDs and was necessary for activation of CD1c-restricted T cells, but

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Pflégr, Václav, Jana Maixnerová, Jiřina Stolaříková, et al. "Design and Synthesis of Highly Active Antimycobacterial Mutual Esters of 2-(2-Isonicotinoylhydrazineylidene)propanoic Acid." Pharmaceuticals 14, no. 12 (2021): 1302. http://dx.doi.org/10.3390/ph14121302.

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The combination of two active scaffolds into one molecule represents a proven approach in drug design to overcome microbial drug resistance. We designed and synthesized more lipophilic esters of 2-(2-isonicotinoylhydrazineylidene)propanoic acid, obtained from antitubercular drug isoniazid, with various alcohols, phenols and thiols, including several drugs, using carbodiimide-mediated coupling. Nineteen new esters were evaluated as potential antimycobacterial agents against drug-sensitive Mycobacterium tuberculosis (Mtb.) H37Rv, Mycobacterium avium and Mycobacterium kansasii. Selected derivativ

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Yokoyama, Kazumasa, Davide Cossu, Yasunobu Hoshino, Yuji Tomizawa, Eiichi Momotani, and Nobutaka Hattori. "Anti-Mycobacterial Antibodies in Paired Cerebrospinal Fluid and Serum Samples from Japanese Patients with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder." Journal of Clinical Medicine 7, no. 12 (2018): 522. http://dx.doi.org/10.3390/jcm7120522.

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Local synthesis of antibodies and presence of oligoclonal bands in the cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS). We investigated the frequency of antibodies against mycobacterial and relevant human epitopes in the CSF of patients with MS or neuromyelitis optica spectrum disorder (NMOSD) and whether these antibodies differed from those present in the serum. Matched serum and CSF samples from 46 patients with MS, 42 patients with NMOSD, and 29 age-matched and sex-matched control subjects were screened retrospectively for the presence of antibodies against Mycobacterium

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Stephanie, Filia, Usman Sumo Friend Tambunan, and Teruna J. Siahaan. "M. tuberculosis Transcription Machinery: A Review on the Mycobacterial RNA Polymerase and Drug Discovery Efforts." Life 12, no. 11 (2022): 1774. http://dx.doi.org/10.3390/life12111774.

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Mycobacterium tuberculosis (MTB) is the main source of tuberculosis (TB), one of the oldest known diseases in the human population. Despite the drug discovery efforts of past decades, TB is still one of the leading causes of mortality and claimed more than 1.5 million lives worldwide in 2020. Due to the emergence of drug-resistant strains and patient non-compliance during treatments, there is a pressing need to find alternative therapeutic agents for TB. One of the important areas for developing new treatments is in the inhibition of the transcription step of gene expression; it is the first s

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Zhang, Lu, Yao Zhao, Ruogu Gao, et al. "Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB2-AcpM2." Protein & Cell 11, no. 7 (2020): 505–17. http://dx.doi.org/10.1007/s13238-020-00726-6.

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Abstract Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its “resting state” and DPA-bound “active state”. EmbB is a fifteen-transme

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Sow, Fatoumata Ba, Larry Schlesinger, Abhay Satoskar, Bruce Zwilling та William Lafuse. "Hepcidin is synergistically induced in mouse macrophages by mycobacteria and IFN-γ, and is present in the mycobacterial phagosome (B166)". Journal of Immunology 178, № 1_Supplement (2007): LB35. http://dx.doi.org/10.4049/jimmunol.178.supp.b166.

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Abstract In mammals, infection results in the production of inflammatory cytokines and acute-phase reactants in the liver, including the synthesis of the antimicrobial peptide, hepcidin. Hepcidin controls extracellular iron by regulating its intestinal absorption and release from macrophages. It acts by binding to and mediating the degradation of the sole iron export protein ferroportin 1. Here, we investigated the expression of hepcidin in mouse macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis H37Rv. We show that stimulation with mycobac

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Sritharan, Manjula. "Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake." Journal of Bacteriology 198, no. 18 (2016): 2399–409. http://dx.doi.org/10.1128/jb.00359-16.

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Mycobacterium tuberculosisrequires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe3+-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival ofM. tuberculosis, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrop

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Kwofie, Samuel K., Kweku S. Enninful, Jaleel A. Yussif, et al. "Molecular Informatics Studies of the Iron-Dependent Regulator (ideR) Reveal Potential Novel Anti-Mycobacterium ulcerans Natural Product-Derived Compounds." Molecules 24, no. 12 (2019): 2299. http://dx.doi.org/10.3390/molecules24122299.

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Buruli ulcer is a neglected tropical disease caused by the bacterium Mycobacterium ulcerans. Its virulence is attributed to the dermo-necrotic polyketide toxin mycolactone, whose synthesis is regressed when its iron acquisition system regulated by the iron-dependent regulator (ideR) is deactivated. Interfering with the activation mechanism of ideR to inhibit the toxin’s synthesis could serve as a possible cure for Buruli ulcer. The three-dimensional structure of the ideR for Mycobacterium ulcerans was generated using homology modeling. A library of 832 African natural products (AfroDB), as wel

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Khetmalis, Yogesh Mahadu, Surendar Chitti, Anjani Umarani Wunnava, et al. "Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-a]pyridine analogues." RSC Medicinal Chemistry 13, no. 3 (2022): 327–42. http://dx.doi.org/10.1039/d1md00367d.

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34 imidazo[1,2-a]pyridine amides & sulfonamides are synthesized & evaluated for in vitro anti-TB activity against MTB H37Rv. IPA-6 is most potent with MIC 0.05 μg mL−1 & 125 times active than ethambutol & docked to MTB enoyl acyl protein reductase.

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Corrêa, Ivan R, Andrea Nören-Müller, Horst-Dieter Ambrosi, et al. "Identification of Inhibitors for Mycobacterial Protein Tyrosine Phosphatase B (MptpB) by Biology-Oriented Synthesis (BIOS)." Chemistry – An Asian Journal 2, no. 9 (2007): 1109–26. http://dx.doi.org/10.1002/asia.200700125.

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Gonzalez-y-Merchand, J. A., M. J. Colston, and R. A. Cox. "Effects of Growth Conditions on Expression of Mycobacterial murA and tyrS Genes and Contributions of Their Transcripts to Precursor rRNA Synthesis." Journal of Bacteriology 181, no. 15 (1999): 4617–27. http://dx.doi.org/10.1128/jb.181.15.4617-4627.1999.

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ABSTRACT All mycobacteria studied to date have an rRNA operon, designatedrrnA, located downstream from a single copy of themurA gene, which encodes an enzyme (EC 2.5.1.7 ) important for peptidoglycan synthesis. The rrnA operon has a promoter, P1(A), located within the coding region of murA, near the 3′ end. Samples of RNA were isolated from Mycobacterium tuberculosis at different stages of the growth cycle and fromMycobacterium smegmatis grown under different conditions. RNase protection assays were used to investigate transcripts of bothmurA and rrnA. Transcription ofmurA was found to continu

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Burke, Christopher, Monika Jankute, Patrick Moynihan, et al. "Development of a novel secondary phenotypic screen to identify hits within the mycobacterial protein synthesis pipeline." FASEB BioAdvances 2, no. 10 (2020): 600–612. http://dx.doi.org/10.1096/fba.2020-00022.

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Sharma, Indra Mani, Sunita Prakash, Thillaivillalan Dhanaraman, and Dipankar Chatterji. "Characterization of a dual-active enzyme, DcpA, involved in cyclic diguanosine monophosphate turnover in Mycobacterium smegmatis." Microbiology 160, no. 10 (2014): 2304–18. http://dx.doi.org/10.1099/mic.0.080200-0.

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We have reported previously that the long-term survival of Mycobacterium smegmatis is facilitated by a dual-active enzyme MSDGC-1 (renamed DcpA), which controls the cellular turnover of cyclic diguanosine monophosphate (c-di-GMP). Most mycobacterial species possess at least a single copy of a DcpA orthologue that is highly conserved in terms of sequence similarity and domain architecture. Here, we show that DcpA exists in monomeric and dimeric forms. The dimerization of DcpA is due to non-covalent interactions between two protomers that are arranged in a parallel orientation. The dimer shows b

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Kapranov, Ivan, S. Bukhdruker, M. Karpova, et al. "Abstract P-11: Microscale Thermophoresis of Mycobacterial Cytochrome P450 with Azole Drugs." International Journal of Biomedicine 11, Suppl_1 (2021): S15—S16. http://dx.doi.org/10.21103/ijbm.11.suppl_1.p11.

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Background: Cytochrome P450 family members are found in most organisms where they are involved in the metabolism and synthesis of steroids, bile acids, unsaturated fatty acids, phenolic metabolites as well as exogenic chemicals. Drugs targeting cytochrome P450 have been shown to inhibit the growth of Mycobacterium tuberculosis, the causative agent of one of the deadliest diseases – tuberculosis. Recently, we showed that CYP124, CYP125, and CYP142 can bind and metabolize a panel of human immunoactive oxysterols in vitro (Varaksa et al., 2021) and one of them (CYP124) can metabolize antitubercul

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Dubois, Eric P., John B. Robbins, and Vince Pozsgay. "Chemical approaches to bacterial vaccines. synthesis of mycobacterial oligosaccharide-protein conjugates for use as serodiagnostics and immunogens." Bioorganic & Medicinal Chemistry Letters 6, no. 12 (1996): 1387–92. http://dx.doi.org/10.1016/0960-894x(96)00235-1.

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Garg, Rajni, Deeksha Tripathi, Sashi Kant, Harish Chandra, Rakesh Bhatnagar, and Nirupama Banerjee. "The Conserved Hypothetical Protein Rv0574c Is Required for Cell Wall Integrity, Stress Tolerance, and Virulence of Mycobacterium tuberculosis." Infection and Immunity 83, no. 1 (2014): 120–29. http://dx.doi.org/10.1128/iai.02274-14.

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The virulence ofMycobacterium tuberculosisis intimately related to its distinctive cell wall. The biological significance of poly-α-l-glutamine (PLG), a component in the cell wall of virulent mycobacteria, has not been explored adequately. The focus of this study is to investigate the role of a locus, Rv0574c, coding for a polyglutamate synthase-like protein, in the synthesis of poly-α-l-glutamine in the context of mycobacterial virulence. Evaluation of Rv0574c gene expression inM. tuberculosisdemonstrated its growth-phase-linked induction with concomitant accumulation of poly-α-l-glutamine in

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Kolly, Gaëlle S., Raju Mukherjee, Emöke Kilacsková, et al. "GtrA Protein Rv3789 Is Required for Arabinosylation of Arabinogalactan in Mycobacterium tuberculosis." Journal of Bacteriology 197, no. 23 (2015): 3686–97. http://dx.doi.org/10.1128/jb.00628-15.

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ABSTRACTMycobacterium tuberculosispossesses a thick and highly hydrophobic cell wall principally composed of a mycolyl-arabinogalactan-peptidoglycan complex, which is critical for survival and virulence. DprE1 is a well-characterized component of decaprenyl-phospho-ribose epimerase, which produces decaprenyl-phospho-arabinose (DPA) for the biosynthesis of mycobacterial arabinans. Upstream ofdprE1liesrv3789, which encodes a short transmembrane protein of the GtrA family, whose members are often involved in the synthesis of cell surface polysaccharides. We demonstrate thatrv3789anddprE1are cotra

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Singh, Kratika, Niharika Pandey, Firoz Ahmad, et al. "Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study." Antibiotics 11, no. 8 (2022): 1038. http://dx.doi.org/10.3390/antibiotics11081038.

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Mycobacterium tuberculosis (M.tb.) enoyl-acyl carrier protein (ACP) reductase (InhA) is validated as a useful target for tuberculosis therapy and is considered an attractive enzyme to drug discovery. This study aimed to identify the novel inhibitor of the InhA enzyme, a potential target of M.tb. involved in the type II fatty acid biosynthesis pathway that controls mycobacterial cell envelope synthesis. We compiled 80 active compounds from Ruta graveolens and citrus plants belonging to the Rutaceae family for pharmacokinetics and molecular docking analyses. The chemical structures of the 80 phy

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Munshi, Tulika, Adam Sparrow, Brendan W. Wren, Rajko Reljic, and Samuel J. Willcocks. "The Antimicrobial Peptide, Bactenecin 5, Supports Cell-Mediated but Not Humoral Immunity in the Context of a Mycobacterial Antigen Vaccine Model." Antibiotics 9, no. 12 (2020): 926. http://dx.doi.org/10.3390/antibiotics9120926.

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Bactenecin (Bac) 5 is a bovine antimicrobial peptide (AMP) capable of killing some species of bacteria through the inhibition of protein synthesis. Bac5 and other AMPs have also been shown to have chemotactic properties and can induce inflammatory cytokine expression by innate immune cells. Recently, AMPs have begun to be investigated for their potential use as novel vaccine adjuvants. In the current work, we characterise the functionality of Bac5 in vitro using murine macrophage-like cells, ex vivo using human tonsil tissue and in vivo using a murine model of vaccination. We report the effect

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