Investigation Into the Biosynthesis and Function of a Novel Sulfomenaquinone from Mycobacterium Tuberculosis

Investigation Into the Biosynthesis and Function of a Novel Sulfomenaquinone from Mycobacterium Tuberculosis
Author: Kimberly Makiko Sogi
Publisher:
Total Pages: 172
Release: 2012
Genre:
ISBN:

Mycobacterium tuberculosis (Mtb) is the leading cause of bacterial deaths worldwide causing two million deaths annually and infects almost one third of the world population. Throughout its lifecycle, Mtb undergoes a series of changes in respiration and metabolic rates. During disease transmission from human to human, the bacteria are in a high respiratory and metabolic rate enabling rapid division. During infection, with the onset of the adaptive immune response, Mtb slows its respiratory and metabolic rates to a non-replicative state. Mtb can persist in this state for years to decades. The delicate balance of the host immune response and Mtb survival is only beginning to be understood. In 2006, we identified a sulfomenaquinone, named S881 for its exact mass, that required the sulfotransferase 3 (stf3) gene for production. A Mtb stf3 mutant exhibited a hypervirulent phenotype in the mouse model of infection. Mice infected with the stf3 mutant, succumbed to infection more rapidly than mice infected with wild type and contained a higher bacterial burden in the lungs. This thesis explores structural characterization of S881 and its biosynthesis and function. Chapter 1 reviews the role of menaquinone, the metabolic precursor to S881, in Mtb, while Chapter 2 discusses the characterization of the S881 structure using high resolution mass spectrometry fragmentation analysis. Chapter 3 discusses the biosynthesis of S881 and investigates the regulation of S881 production. Using the S881 mutants, Chapter 4 explores various models of Mtb infection to study the function of S881. Finally Chapter 5 describes the initial characterization of the promoter for S881 genes to understand S881 genetic regulation.

Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0

Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0
Author: Patrick M. Dansette
Publisher: MDPI
Total Pages: 286
Release: 2021-08-31
Genre: Science
ISBN: 3036502564

This book, "Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity", presents five papers on human cytochrome P450 (CYP) and P450 reductase, three reviews on the role of CYPs in humans and their use as biomarkers, six papers on CYPs in microorganisms, and one study on CYP in insects. The first paper reports the in silico modeling of human CYP3A4 access channels. The second uses structural methods to explain the mechanism-based inactivation of CYP3A4 by mibefradil, 6,7-dihydroxy-bergamottin, and azamulin. The third article compares electron transfer in CYP2C9 and CYP2C19 using structural and biochemical methods, and the fourth uses kinetic methods to study electron transfer to CYP2C8 allelic mutants. The fifth article characterizes electron transfer between the reductase and CYP using in silico and in vitro methods, focusing on the conformations of the reductase. Then, two reviews describe clinical implications in cardiology and oncology and the role of fatty acid metabolism in cardiology and skin diseases. The second review is on the potential use of circulating extracellular vesicles as biomarkers. Five papers analyze the CYPomes of diverse microorganisms: the Bacillus genus, Mycobacteria, the fungi Tremellomycetes, Cyanobacteria, and Streptomyces. The sixth focuses on a specific Mycobacterium CYP, CYP128, and its importance in M. tuberculosis. The subject of the last paper is CYP in Sogatella furcifera, a plant pest, and its resistance to the insecticide sulfoxaflor.

Tuberculosis and the Tubercle Bacillus

Tuberculosis and the Tubercle Bacillus
Author: William R. Jacobs, Jr.
Publisher: John Wiley & Sons
Total Pages: 1379
Release: 2017-09-01
Genre: Medical
ISBN: 1683673050

Can today's innovative practices and molecular tools tame this ancient disease? One third of the world's population is infected with tuberculosis (TB), with about 10 million new cases annually. To combat TB and its agent, Mycobacterium tuberculosis, the World Health Organization launched The End TB Strategy, which aims to slash the suffering and cost of TB by 2035. This makes the second edition of Tuberculosis and the Tubercle Bacillus, edited by Jacobs, McShane, Mizrahi, and Orme, an extremely valuable resource for scientists and clinicians. The editors have gathered their colleagues from around the world to present the latest on the molecular biology of M. tuberculosis and related species, the host-pathogen interactions that enable invasion, and the host's immune response to M. tuberculosis infection. The basic, clinical, and translational research presented in this book supports the goals of WHO's End TB Strategy by driving toward the development of effective vaccines, rapid molecular diagnostics, and anti-TB drugs. Creating an effective tuberculosis vaccine. Understand the innate and adaptive immune response to M. tuberculosis infection, its study in established animal models, and how this information is being used to develop new vaccines against TB. Formulating new antituberculosis drugs. Learn the challenges and methods for evaluating new drugs in preclinical trials with a focus on drugs that work against "persisters" and those that act on the electron transport complex and ATP synthase of M. tuberculosis. Overcoming the challenges of diagnosing tuberculosis. Review new diagnostic tools that are simple, rapid, affordable, specific, sensitive, and safe, including molecular-based diagnostic methods such as GeneXpert MTB/RIF. Using molecular, genomic, and bioinformatics tools to understand the biology and evolution of Mycobacterium. Explore current research on the molecular mechanisms that M. tuberculosis uses to evade the immune system, enter a state of nonreplicating persistence, and become reactivated. The second edition of Tuberculosis and the Tubercle Bacillus presents the latest research on a microorganism that is exquisitely well adapted to its human host. This pathogen continues to confound scientists, clinicians, and public health specialists, who will all find much valuable information in this comprehensive set of reviews.

Molecular Genetics of Mycobacteria

Molecular Genetics of Mycobacteria
Author: Graham F. Hatfull
Publisher: John Wiley & Sons
Total Pages: 1428
Release: 2014-09-02
Genre: Science
ISBN: 1683673425

A comprehensive collection of perspectives by experts in mycobacterial molecular biology Mycobacterium tuberculosis causes one in four avoidable deaths in the developing world and kills more adults than malaria, AIDS, and all tropical diseases combined. Tuberculosis was named a global health emergency by the World Health Organization, a distinction no other disease has received. Although the study of mycobacterial genetics has expanded dramatically, with new investigations into mycobacterial growth, replication, metabolism, physiology, drug susceptibility, and virulence, most of the problems in tuberculosis control that existed in 2000 remain today. Advances in our understanding of mycobacterial genetics have been reflected in exciting recent developments. New diagnostic approaches can identify drug resistance within a few hours, promising new drugs are progressing through the pipeline and into the clinic, and a range of newly developed vaccines are being evaluated. It is an exciting time as the fruits of 30 years of intensive genetic investigation are finally beginning to emerge. Written by leading experts in the field, Molecular Genetics of Mycobacteria, Second Edition, Discusses key areas of current research in mycobacterial genetics Explains the genetics of the physiology, metabolism, and drug sensitivities of M. tuberculosis Presents genetic approaches for manipulating M. tuberculosis This book is an invaluable resource for anyone interested in the molecular genetics and molecular biology of mycobacteria.

Molecular Microbial Ecology Manual

Molecular Microbial Ecology Manual
Author: Antoon D. L. Akkermans
Publisher: Springer
Total Pages: 266
Release: 2014-01-13
Genre: Science
ISBN: 9400902158

For a long time microbial ecology has been developed as a distinct field within Ecology. In spite of the important role of microorganisms in the environment, this group of 'invisible' organisms remained unaccessable to other ecologists. Detection and identification of microorganisms remain largely dependent on isolation techniques and characterisation of pure cul tures. We now realise that only a minor fraction of the microbial com munity can be cultivated. As a result of the introduction of molecular methods, microbes can now be detected and identified at the DNA/RNA level in their natural environment. This has opened a new field in ecology: Molecular Microbial Ecology. In the present manual we aim to introduce the microbial ecologist to a selected number of current molecular techniques that are relevant in micro bial ecology. The first edition of the manual contains 33 chapters and an equal number of additional chapters will be added this year. Since the field of molecular ecology is in a continuous progress, we aim to update and extend the Manual regularly and will invite anyone to depo sit their new protocols in full detail in the next edition of this Manual. We hope this book finds its place where it was born: at the lab bench! Antoon D.L. Akkermans, Jan Dirk van Elsas and Frans J. de Bruijn March 1995 Molecular Microbial Ecology Manual 1.3.6: 1-8, 1996. © 1996 Kluwer Academic Publishers.

Peroxisomes and their Key Role in Cellular Signaling and Metabolism

Peroxisomes and their Key Role in Cellular Signaling and Metabolism
Author: Luis A. del Río
Publisher: Springer Science & Business Media
Total Pages: 353
Release: 2013-07-03
Genre: Medical
ISBN: 9400768893

Peroxisomes are a class of ubiquitous and dynamic single membrane-bounded cell organelles, devoid of DNA, with an essentially oxidative type of metabolism. In recent years it has become increasingly clear that peroxisomes are involved in a range of important cellular functions in almost all eukaryotic cells. In higher eukaryotes, including humans, peroxisomes catalyze ether phospholipids biosynthesis, fatty acid alpha-oxidation, glyoxylate detoxification, etc, and in humans peroxisomes are associated with several important genetic diseases. In plants, peroxisomes carry out the fatty acid beta-oxidation, photorespiration, metabolism of ROS, RNS and RSS, photomorphogenesis, biosynthesis of phytohormones, senescence, and defence against pathogens and herbivores. In recent years it has been postulated a possible contribution of peroxisomes to cellular signaling. In this volume an updated view of the capacity and function of peroxisomes from human, animal, fungal and plant origin as cell generators of different signal molecules involved in distinct processes of high physiological importance is presented.

On Epidemics

On Epidemics
Author: Hippocrates
Publisher: Good Press
Total Pages: 52
Release: 2021-04-10
Genre: Nature
ISBN:

"On Epidemics" by Hippocrates (translated by Francis Adams). Published by Good Press. Good Press publishes a wide range of titles that encompasses every genre. From well-known classics & literary fiction and non-fiction to forgotten−or yet undiscovered gems−of world literature, we issue the books that need to be read. Each Good Press edition has been meticulously edited and formatted to boost readability for all e-readers and devices. Our goal is to produce eBooks that are user-friendly and accessible to everyone in a high-quality digital format.

The Mycobacterial Cell Envelope

The Mycobacterial Cell Envelope
Author: Mamadou Daffé
Publisher:
Total Pages: 0
Release: 2008
Genre: Bacterial cell walls
ISBN: 9781555814687

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.