The Role of Sulfated Metabolites in the Pathogenesis of Mycobacterium Tuberculosis PDF Download
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Author: Sarah Anne Gilmore
Publisher:
ISBN:
Category :
Languages : en
Pages : 316
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Author: Sarah Anne Gilmore
Publisher:
ISBN:
Category :
Languages : en
Pages : 316
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Book Description
Author: Joseph David Mougous
Publisher:
ISBN:
Category :
Languages : en
Pages : 342
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Author: Michael William Schelle
Publisher:
ISBN:
Category :
Languages : en
Pages : 376
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Author: Cynthia Michelle Holsclaw
Publisher:
ISBN: 9781124508818
Category :
Languages : en
Pages :
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Book Description
A number of unique metabolites contribute to the virulence of the human pathogen Mycobacterium tuberculosis, the primary causative agent of tuberculosis. Mycobacterium tuberculosis synthesizes a formidable, highly lipid-rich cell envelope, which non-covalently associates with cell surface-exposed lipids specific to pathogenic mycobacteria. Many of these lipids have been linked to the virulence and pathogenesis of the bacterium. However detailing the precise biochemical functions of these metabolites remains an active area of investigation. Determining the detailed chemical structures of these metabolites and elucidating the biosynthetic pathways leading to their production are essential to further our understanding of their specific functions. Therefore, the focus of the research presented in this thesis is to determine the detailed chemical structures and biosynthetic pathways of key Mycobacterium tuberculosis metabolites, as well as to improve the current methodology in the analysis of these compounds. Chapter 1 describes the biology of Mycobacterium tuberculosis and provides a historical background of the investigations into the metabolites further studied in this thesis. This chapter also provides a detailed review of the mass spectrometry techniques essential to the research performed in these studies. Chapter 2 describes the detailed structural characterization of the novel sulfated menaquinone S881, a negative regulator of Mycobacterium tuberculosis virulence. An investigation into the biosynthesis of another cell-surface lipid, polyacyltrehalose, is detailed in Chapter 3. Chapter 4 describes the development of a rapid mass spectrometry-based method to relatively quantitate the mycobacterium-specific redox metabolite mycothiol across different strains of Mycobacterium smegmatis. Finally, Chapter 5 investigates the high-resolution MS analysis of M. tuberculosis cell-surface metabolites, with a focus on the results obtained between two different high-resolution instruments. This study also describes the analysis of S881 levels across five strains of Mycobacterium tuberculosis with differing levels of virulence, as well as the vaccine strain Mycobacterium bovis BCG.
Author: Stephanie Stuteley
Publisher:
ISBN:
Category : Antitubercular agents
Languages : en
Pages : 158
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Book Description
Tuberculosis (TB) infects up to one third of the world’s population and, as one of the leading killers of humans, it is imperative to understand its pathogenic mechanisms. Key to the success of the causative agent, Mycobacterium tuberculosis (Mtb), is its ability to transition into an undetectable latent state that it may remain in for decades. Fe-S clusters are an essential component in Mtb metabolism and have been identified as playing a role in sensing and responding to the harsh environmental conditions, such as the oxidative and nitrosative stress and iron starvation, imposed on Mtb by the host immune system. While the regulation of Fe-S biogenesis in Gram-negative bacteria is well understood, less is known about this process in Mtb. Research in our laboratory has identified a putative transcriptional regulator of Fe-S cluster biogenesis in Mtb, SufR, which is the main subject of my research. This protein is highly expressed in both patient derivedsamples and infection models, leading us to believe that the regulation of Fe-S cluster biogenesis plays an important role in TB pathogenesis. During this research, I showed that SufR potentially binds [4Fe-4S] clusters and identified a DNA binding element that SufR preferentially binds in the presence of the intact clusters. This binding sequence is located within the putative coding region of SufR, suggesting that the original SufR open reading frame may be misannotated. Intriguingly, Mtb-SufR is a monomer in solution and dimerises upon DNA binding, potentially adding another level of control via protein association. While crystallisation experiments yielded promising brown coloured crystals of SufR in the presence of regulatory DNA, they did not diffract to a resolution useful for structural determination. One of the significant uses of Fe-S clusters in Mtb is in the formation of the catalytic chromophore (F0)of F420, a cofactor which has been shown to have protective antioxidant properties. Biosynthesis of F0is carried out by the enzyme FbiC which contains two [4Fe-4S] radical SAM active sites. While a reaction mechanism has been proposed based on the investigation of homologues from other species, this research reports the first soluble production of FbiC from mycobacteria.
Author: Mamadou Daffé
Publisher:
ISBN: 9781555814687
Category : Bacterial cell walls
Languages : en
Pages : 0
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Book Description
Explains the unique characteristics that cause this large group of bacteria responsible for tuberculosis and leprosy to function differently; serves as a valuable reference for those working in the areas of biochemistry, genetics, genomics, and immunology.
Author: National Academy of Sciences (U.S.)
Publisher:
ISBN:
Category : Electronic journals
Languages : en
Pages : 1456
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Book Description
Author:
Publisher: Academic Press
ISBN: 0080923364
Category : Science
Languages : en
Pages : 644
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Book Description
Microbial natural products have been an important traditional source of valuable antibiotics and other drugs but interest in them waned in the 1990s when big pharma decided that their discovery was no longer cost-effective and concentrated instead on synthetic chemistry as a source of novel compounds, often with disappointing results. Moreover understanding the biosynthesis of complex natural products was frustratingly difficult. With the development of molecular genetic methods to isolate and manipulate the complex microbial enzymes that make natural products, unexpected chemistry has been revealed and interest in the compounds has again flowered. This two-volume treatment of the subject will showcase the most important chemical classes of complex natural products: the peptides, made by the assembly of short chains of amino acid subunits, and the polyketides, assembled from the joining of small carboxylic acids such as acetate and malonate. In both classes, variation in sub-unit structure, number and chemical modification leads to an almost infinite variety of final structures, accounting for the huge importance of the compounds in nature and medicine. Gathers tried and tested methods and techniques from top players in the field Provides an extremely useful reference for the experienced research scientist Covers biosynthesis of Polyketides, Tarpenoids, Aminocoumarins and Crabohydrates
Author:
Publisher: Academic Press
ISBN: 0080951147
Category : Science
Languages : en
Pages : 215
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Book Description
Published since 1959, Advances in Applied Microbiology continues to be one of the most widely read and authoritative review sources in microbiology. The series contains comprehensive reviews of the most current research in applied microbiology. Recent areas covered include bacterial diversity in the human gut, protozoan grazing of freshwater biofilms, metals in yeast fermentation processes and the interpretation of host-pathogen dialogue through microarrays. Eclectic volumes are supplemented by thematic volumes on various topics, including Archaea and sick building syndrome. Impact factor for 2007: 1.821. - Contributions from leading authorities and industry experts - Informs and updates on all the latest developments in the field - Reference and guide for scientists and specialists involved in advancements in applied microbiology
Author: Jean-Claude Bertrand
Publisher: Springer
ISBN: 940179118X
Category : Science
Languages : en
Pages : 933
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Book Description
This book is a treatise on microbial ecology that covers traditional and cutting-edge issues in the ecology of microbes in the biosphere. It emphasizes on study tools, microbial taxonomy and the fundamentals of microbial activities and interactions within their communities and environment as well as on the related food web dynamics and biogeochemical cycling. The work exceeds the traditional domain of microbial ecology by revisiting the evolution of cellular prokaryotes and eukaryotes and stressing the general principles of ecology. The overview of the topics, authored by more than 80 specialists, is one of the broadest in the field of environmental microbiology. The overview of the topics, authored by more than 80 specialists, is one of the broadest in the field of environmental microbiology.
