96 results found
Butler RE, Krishnan N, Garcia-Jimenez W, et al., 2017, Susceptibility of M. tuberculosis-infected host cells to phospho-MLKL driven necroptosis is dependent on cell type and presence of TNFα., Virulence
An important feature of Mycobacterium tuberculosis pathogenesis is the ability to control cell death in infected host cells, including inhibition of apoptosis and stimulation of necrosis. Recently an alternative form of programmed cell death, necroptosis, has been described where necrotic cell death is induced by apoptotic stimuli under conditions where apoptotic execution is inhibited. We show for the first time that M. tuberculosis and TNFα synergise to induce necroptosis in murine fibroblasts via RIPK1-dependent mechanisms and characterized by phosphorylation of Ser345 of the MLKL necroptosis death effector. However, in murine macrophages M. tuberculosis and TNFα induce non-necroptotic cell death that is RIPK1-dependent but independent of MLKL phosphorylation. Instead, M. tuberculosis-infected macrophages undergo RIPK3-dependent cell death which occurs both in the presence and absence of TNFα and involves the production of mitochondrial ROS. Immunocytochemical staining for MLKL phosphorylation further demonstrated the occurrence of necroptosis in vivo in murine M. tuberculosis granulomas. Phosphorylated-MLKL immunoreactivity was observed associated with the cytoplasm and nucleus of fusiform cells in M. tuberculosis lesions but not in proximal macrophages. Thus whereas pMLKL-driven necroptosis does not appear to be a feature of M. tuberculosis-infected macrophage cell death, it may contribute to TNFα-induced cytotoxicity of the lung stroma and therefore contribute to necrotic cavitation and bacterial dissemination.
Khara JS, Obuobi S, Wang Y, et al., 2017, Disruption of drug-resistant biofilms using de novo designed short alpha-helical antimicrobial peptides with idealized facial amphiphilicity, ACTA BIOMATERIALIA, Vol: 57, Pages: 103-114, ISSN: 1742-7061
Priestman M, Thomas P, Robertson BD, et al., 2017, Mycobacteria Modify Their Cell Size Control under Sub-Optimal Carbon Sources., Front Cell Dev Biol, Vol: 5, ISSN: 2296-634X
The decision to divide is the most important one that any cell must make. Recent single cell studies suggest that most bacteria follow an "adder" model of cell size control, incorporating a fixed amount of cell wall material before dividing. Mycobacteria, including the causative agent of tuberculosis Mycobacterium tuberculosis, are known to divide asymmetrically resulting in heterogeneity in growth rate, doubling time, and other growth characteristics in daughter cells. The interplay between asymmetric cell division and adder size control has not been extensively investigated. Moreover, the impact of changes in the environment on growth rate and cell size control have not been addressed for mycobacteria. Here, we utilize time-lapse microscopy coupled with microfluidics to track live Mycobacterium smegmatis cells as they grow and divide over multiple generations, under a variety of growth conditions. We demonstrate that, under optimal conditions, M. smegmatis cells robustly follow the adder principle, with constant added length per generation independent of birth size, growth rate, and inherited pole age. However, the nature of the carbon source induces deviations from the adder model in a manner that is dependent on pole age. Understanding how mycobacteria maintain cell size homoeostasis may provide crucial targets for the development of drugs for the treatment of tuberculosis, which remains a leading cause of global mortality.
Khara JS, Priestman M, Uhia I, et al., 2016, Unnatural amino acid analogues of membrane-active helical peptides with anti-mycobacterial activity and improved stability, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 71, Pages: 2181-2191, ISSN: 0305-7453
Al Shammari B, Shiomi T, Tezera L, et al., 2015, The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis, JOURNAL OF INFECTIOUS DISEASES, Vol: 212, Pages: 463-473, ISSN: 0022-1899
Berg S, Schelling E, Hailu E, et al., 2015, Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection, BMC Infectious Diseases, Vol: 15, ISSN: 1471-2334
Comas I, Hailu E, Kiros T, et al., 2015, Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa, CURRENT BIOLOGY, Vol: 25, Pages: 3260-3266, ISSN: 0960-9822
Joyce G, Robertson BD, Williams KJ, 2015, A modified agar pad method for mycobacterial live-cell imaging., BMC Research Notes, Vol: 4, ISSN: 1756-0500
BACKGROUND: Two general approaches to prokaryotic live-cell imaging have been employed to date, growing bacteria on thin agar pads or growing bacteria in micro-channels. The methods using agar pads 'sandwich' the cells between the agar pad on the bottom and a glass cover slip on top, before sealing the cover slip. The advantages of this technique are that it is simple and relatively inexpensive to set up. However, once the cover slip is sealed, the environmental conditions cannot be manipulated. Furthermore, desiccation of the agar pad, and the growth of cells in a sealed environment where the oxygen concentration will be in gradual decline, may not permit longer term studies such as those required for the slower growing mycobacteria. FINDINGS: We report here a modified agar pad method where the cells are sandwiched between a cover slip on the bottom and an agar pad on top of the cover slip (rather than the reverse) and the cells viewed from below using an inverted microscope. This critical modification overcomes some of the current limitations with agar pad methods and was used to produce time-lapse images and movies of cell growth for Mycobacterium smegmatis and Mycobacterium bovis BCG. CONCLUSIONS: This method offers improvement on the current agar pad methods in that long term live cell imaging studies can be performed and modification of the media during the experiment is permitted.
Williams KJ, Jenkins VA, Barton GR, et al., 2015, Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress., Molecular Microbiology, Vol: 97, Pages: 1142-1157, ISSN: 1365-2958
A key component to the success of Mycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M. tuberculosis. In this study we have used transcriptomics and ChIP-seq to address this. In response to nitrogen starvation a total of 185 genes were significantly differentially expressed (96 up-regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M. tuberculosis to that in non-pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging.
Sampson SL, Saraiva L, Gustafsson K, et al., 2014, Cell Electrospinning: An In Vitro and In Vivo Study, SMALL, Vol: 10, Pages: 78-82, ISSN: 1613-6810
Al Shammari B, Shiomi T, Tezera L, et al., 2013, Cell-matrix interactions regulate the immune response to Mycobacterium tuberculosis, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 104-104, ISSN: 0019-2805
Andreu N, Zelmer A, Sampson SL, et al., 2013, Rapid in vivo assessment of drug efficacy against Mycobacterium tuberculosis using an improved firefly luciferase, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 68, Pages: 2118-2127, ISSN: 0305-7453
Arafah S, Kicka S, Trofimov V, et al., 2013, Setting up and monitoring an infection of Dictyostelium discoideum with mycobacteria., Methods Mol Biol, Vol: 983, Pages: 403-417
Mycobacterium marinum is the causative agent of fish and amphibian tuberculosis in the wild. It is a genetically close cousin of Mycobacterium tuberculosis, and thereby the infection process remarkably shares many of the hallmarks of M. tuberculosis infection in human, at both the cellular and organism levels. Therefore, M. marinum is used as a model for the study of mycobacterial infection in various host organisms. Recently, the Dictyostelium-M. marinum system has been shown to be a valuable model that recapitulates the main features of the intracellular fate of M. marinum including phagosome maturation arrest, as well as its particular cell-to-cell dissemination mode. We present here a "starter kit" of detailed methods that allows to establish an infection of Dictyostelium with M. marinum and to monitor quantitatively the intracellular bacterial growth.
Firdessa R, Berg S, Hailu E, et al., 2013, Mycobacterial Lineages Causing Pulmonary and Extrapulmonary Tuberculosis, Ethiopia, EMERGING INFECTIOUS DISEASES, Vol: 19, Pages: 460-463, ISSN: 1080-6040
Jenkins VA, Barton GR, Robertson BD, et al., 2013, Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis, BMC GENOMICS, Vol: 14, ISSN: 1471-2164
Krishnan N, Robertson BD, Thwaites G, 2013, Pathways of IL-1 beta secretion by macrophages infected with clinical Mycobacterium tuberculosis strains, TUBERCULOSIS, Vol: 93, Pages: 538-547, ISSN: 1472-9792
Tsolaki AG, Nagy J, Leiva S, et al., 2013, Mycobacterium tuberculosis antigen 85B and ESAT-6 expressed as a recombinant fusion protein in Mycobacterium smegmatis elicits cell-mediated immune response in a murine vaccination model, MOLECULAR IMMUNOLOGY, Vol: 54, Pages: 278-283, ISSN: 0161-5890
Williams KJ, Bennett MH, Barton GR, et al., 2013, Adenylylation of mycobacterial Glnk (PII) protein is induced by nitrogen limitation, TUBERCULOSIS, Vol: 93, Pages: 198-206, ISSN: 1472-9792
Williams KJ, Bryant WA, Jenkins VA, et al., 2013, Deciphering the response of Mycobacterium smegmatis to nitrogen stress using bipartite active modules, BMC GENOMICS, Vol: 14, ISSN: 1471-2164
Andreu N, Fletcher T, Krishnan N, et al., 2012, Rapid measurement of antituberculosis drug activity in vitro and in macrophages using bioluminescence, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 67, Pages: 404-414, ISSN: 0305-7453
Andreu N, Thomas D, Saraiva L, et al., 2012, In Vitro and In Vivo Interrogation of Bio-sprayed Cells, SMALL, Vol: 8, Pages: 2495-2500, ISSN: 1613-6810
Behrends V, Williams KJ, Jenkins VA, et al., 2012, Free Glucosylglycerate Is a Novel Marker of Nitrogen Stress in Mycobacterium smegmatis, JOURNAL OF PROTEOME RESEARCH, Vol: 11, Pages: 3888-3896, ISSN: 1535-3893
Butler RE, Brodin P, Jang J, et al., 2012, The Balance of Apoptotic and Necrotic Cell Death in Mycobacterium tuberculosis Infected Macrophages Is Not Dependent on Bacterial Virulence, PLOS ONE, Vol: 7, ISSN: 1932-6203
Gideon HP, Wilkinson KA, Rustad TR, et al., 2012, Bioinformatic and Empirical Analysis of Novel Hypoxia-Inducible Targets of the Human Antituberculosis T Cell Response, JOURNAL OF IMMUNOLOGY, Vol: 189, Pages: 5867-5876, ISSN: 0022-1767
Jenkins VA, Robertson BD, Williams KJ, 2012, Aspartate D48 is essential for the GlnR-mediated transcriptional response to nitrogen limitation in Mycobacterium smegmatis, FEMS MICROBIOLOGY LETTERS, Vol: 330, Pages: 38-45, ISSN: 0378-1097
Joyce G, Williams KJ, Robb M, et al., 2012, Cell Division Site Placement and Asymmetric Growth in Mycobacteria, PLOS ONE, Vol: 7, ISSN: 1932-6203
Robertson BD, Altmann D, Barry C, et al., 2012, Detection and treatment of subclinical tuberculosis, TUBERCULOSIS, Vol: 92, Pages: 447-452, ISSN: 1472-9792
Robertson BD, Wren B, 2012, Systems Microbiology, Publisher: Caister Academic Pr, ISBN: 9781908230027
Topics covered include mathematical models for systems biology, systems biology of Escherichia coli metabolism, bacterial chemotaxis, systems biology of infection, host-microbe interactions, phagocytosis, system-level study of metabolism in ...
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