Catabolite Sensing Regulatory Pathtways In Group A Streptocccus Control Virulence And Host Pathogen Interactions
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Catabolite Sensing Regulatory Pathtways In Group A Streptocccus Control Virulence And Host Pathogen Interactions
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Author : Colin Christopher Kietzman
language : en
Publisher:
Release Date : 2010
Catabolite Sensing Regulatory Pathtways In Group A Streptocccus Control Virulence And Host Pathogen Interactions written by Colin Christopher Kietzman and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Electronic dissertations categories.
As a pathogen Streptococcus pyogenes (Group A streptococcus) is remarkable for its ability to cause a wide range of diseases and infect hundreds of millions of people yearly. Group A streptococcus faces a unique challenge in its pathogenesis cycle in that humans are its only known reservoir, and colonization and infection commonly occur in the same tissue. Thus to persist within a specific host niche Group A streptococcus has developed a sizable arsenal of effectors and control mechanisms allowing it to combat and adapt to the host immune response. In most cases alteration of regulatory pathways controlling transcription of virulence factor genes leads to significant changes in the ability of Group A streptococcus to cause disease. Several environmental signals and regulators effecting expression of virulence factors have been identified. One of the most pervasive signals effecting streptococcal virulence factor transcription is growth phase. In virtually all described incidences, virulence factor transcript abundance is influenced by growth phase, yet specific signals and mechanisms of sensing growth phase have remained elusive. These studies were undertaken to study the mechanisms of growth phase dependent transcriptional regulation of Group A streptococcal virulence factors, to ii elucidate global changes in transcriptional control due to altered growth phase regulators, and to examine the role of growth phase regulation in host- pathogen interactions during streptococcal infection. In pursuit of these goals, we initially analyzed a growth phase controlled physiologic trait, the production of H2O2, linked to virulence in related pathogens. We identified the gene responsible for H2O2 production, lactate oxidase (IctO), and through transcriptional and biochemical analyses identified the carbon catabolite control protein (CcpA) as a central transcriptional regulator of growth phase in response to glucose availability. Inactivation of CcpA revealed global changes in virulence factor transcription and overlap with another recently identified carbohydrate regulator, LacD1. Studies on these regulators indicated that while they respond to a common signal their effects on co- regulated genes are restricted to discrete times during streptococcal infection. Disruption of CcpA in particular led to attenuation of virulence and mis-regulation of a large contingent of virulence genes in infected tissues. Mis-regulation of target genes in the CcpA mutant correlated with an increase in host TNF[alpha] transcription, and occurred at times when wild type streptococci were causing maximal disease. Ablation of TNF[alpha] in the host led to an increase in local virulence in the CcpA deficient strain, and a switch from local to invasive disease during infection by wild type streptococci. In total, our studies have shown that growth phase regulation is comprised of multiple overlapping and organized pathways. Furthermore, functional growth phase regulation is necessary for Group A streptococcus to cause fully virulent disease, perhaps due to the interaction of growth phase regulated factors with host immune signaling pathways. Finally we have shown that TNF[alpha] is necessary to control localized infection and prevent dissemination to deeper tissues during infections by a streptococcal strain that normally causes localized non- spreading lesions. Understanding the mechanisms by which Group A streptococcus senses the host environment and interacts with the immune system is especially critical in studies of streptococcal pathogenesis and development of anti-streptococcal therapies. A broad spectrum streptococcal protective vaccine is unavailable and without treatment relatively minor streptococcal infections can progress to life threatening invasive disease or lead to highly disabling nonsuppurative sequelae. Our studies suggest that targeting growth phase sensitive regulatory pathways is a good strategy in combating streptococcal disease. In addition, in light of the use of many immunosuppressive therapies as treatments for various ailments, our results indicate the need for further investigations into the role TNF[alpha] in controlling human streptococcal diseases; patients receiving anti-TNF[alpha] treatments may be at an increased risk for serious infections by Group A streptococcus. Further analysis and identification of specific growth phase controlled factors contributing to attenuation of CcpA deficient strains, identification of factors involved in alteration of host-pathogen interactions resulting in disparate TNF[alpha] responses, and elucidation of the mechanisms by which TNF[alpha] production leads to control of localized infection will provide insights into Gram positive bacterial infection, and the molecular mechanisms determining the outcome of Group A streptococcal disease.
Host Pathogen Interactions In Streptococcal Diseases
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Author : G Singh Chhatwal
language : en
Publisher: Springer Science & Business Media
Release Date : 2014-07-08
Host Pathogen Interactions In Streptococcal Diseases written by G Singh Chhatwal and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-08 with Medical categories.
Streptococci are Gram-positive bacteria that cause a wide spectrum of diseases, such as pharyngitis, necrotizing fasciitis and streptococcal toxic shock syndrome, as well as rheumatic fever and rheumatic heart disease as sequelae. Antibiotics alone have not been able to control the disease and in spite of many efforts an effective vaccine is not yet available. A prerequisite for novel and successful strategies for combating these bacteria is a complete understanding of the highly complex pathogenic mechanisms involved, which are analyzed in this volume. In ten chapters, prominent authors cover various aspects including streptococcal diseases and global burden, epidemiology, adaptation and transmission, and molecular mechanisms of different diseases, as well as sequelae, vaccine development and clinical management. This book will serve as a valuable reference work for scientists, students, clinicians and public health workers and provide new approaches to meeting the challenge of streptococcal diseases.
Streptococcus Pneumoniae
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Author : Jeremy Brown
language : en
Publisher: Academic Press
Release Date : 2015-05-08
Streptococcus Pneumoniae written by Jeremy Brown and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-05-08 with Science categories.
Streptococcus Pneumoniae: Molecular Mechanisms of Host-Pathogen Interactions provides a comprehensive overview of our existing knowledge on Streptococcus pneumoniae antibiotic resistance, dissemination, and pathogenesis, including immunology. It presents a state-of-the-art overview of the implications of existing data, along with the areas of research that are important for future insights into the molecular mechanisms of pneumococcal infections and how to combat these infections. Users will find a timely update on the topic, as the dramatic increase in antibiotic resistance pneumoniae cases and limitations of the currently available pneumoniae vaccines are creating new concerns on these gram-positive bacteria that are endowed with a high virulence potential, and are the most common etiologic agent of respiratory and life-threatening invasive diseases. - Provides an updated overview of our existing knowledge on Streptococcus pneumoniae antibiotic resistance, dissemination, and pathogenesis, including immunology - Helps strengthen interdisciplinary networking and the focus of scientific resources by targeting epidemiology, vaccines, genetics, antibiotic resistance, clonal dissemination, Streptococcus pneumoniae biology, functional genomics, inflammasome, biomarkers, and more - Multi-authored by leaders in the field who present a state-of-the-art overview of what the implications are of existing data, and the areas of research that are important for future insights into the molecular mechanisms of pneumococcal infections - Supports combinatory networking in order to find new solutions in clinical therapies - Reflects the most topical pneumococcal research trends
Cumulated Index Medicus
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Author :
language : en
Publisher:
Release Date : 1994
Cumulated Index Medicus written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1994 with Medicine categories.
Microbiology Abstracts
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Author :
language : en
Publisher:
Release Date : 1989
Microbiology Abstracts written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1989 with Industrial microbiology categories.
Biomedical Index To Phs Supported Research
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Author :
language : en
Publisher:
Release Date : 1987
Biomedical Index To Phs Supported Research written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1987 with Medicine categories.
Biomedical Index To Phs Supported Research Pt A Subject Access A H
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Author :
language : en
Publisher:
Release Date : 1994
Biomedical Index To Phs Supported Research Pt A Subject Access A H written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1994 with Medicine categories.
Research Awards Index
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Author :
language : en
Publisher:
Release Date :
Research Awards Index written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on with Medicine categories.
Research Grants Index
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Author : National Institutes of Health (U.S.). Division of Research Grants
language : en
Publisher:
Release Date : 1970
Research Grants Index written by National Institutes of Health (U.S.). Division of Research Grants and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1970 with Medicine categories.
Chemical Abstracts
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Author :
language : en
Publisher:
Release Date : 2002
Chemical Abstracts written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Chemistry categories.