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Elucidating Factors Affecting H-NS-mediated Regulation of Horizontally Acquired Genes in Vibrio Cholerae

Elucidating Factors Affecting H-NS-mediated Regulation of Horizontally Acquired Genes in Vibrio Cholerae PDF Author: Aaron Ross Conrado
Publisher:
ISBN:
Category :
Languages : en
Pages : 198

Book Description
Horizontal gene transfer amongst bacteria plays a critical role in the evolution, emergence, and virulence of both currently recognized and novel pathogens. Vibrio cholerae exemplifies this process, as benign environmental isolates emerge as pandemic pathogens through the acquisition and incorporation of genetic elements encoding virulence factors into their progenitor genomes. In V. cholerae, these genes are localized to distinct areas of the chromosome, known as horizontally acquired islands (HAIs), which are characterized by a lower GC-content than the progenitor genome. In cholera and many other Gram-negative enterics, AT-rich DNA is bound by the H-NS protein immediately upon entrance into the cell, silencing the expression of this potentially toxic DNA. In other enterics, some proteins can remove H-NS from the DNA, allowing the cell to probe these novel genes, while others can interact with H-NS to maintain regulatory control and ensure derepression only happens when appropriate. However, such interactions with H-NS have not been observed in V. cholerae. Here, we discover and characterization of the genetic relationships between H-NS and an H-NS antagonist (ToxR, an essential protein for virulence), as well as an H-NS enhancer (TsrA, a poorly understood protein) in V. cholerae. ToxR is known to be a master activator of virulence, but we demonstrate that ToxR’s critical role is not direct activation, but rather to antagonize H-NS binding at shared binding loci related to host colonization and biofilm formation. Furthermore, TsrA, previously shown to be involved in regulation of type-VI secretion, was detected through immunoprecipitation of H-NS, followed by LC-MS/MS. Subsequent genetic analyses revealed that TsrA enhances H-NS repression of virulence genes on HAIs. Interestingly, TsrA enhances H-NS enrichment at areas of low-GC content, similar to the H-NS interactors in other enterics that V. cholerae was thought to lack. TsrA deletion also affects uptake of a mobile genetic element, establishing the first Vibrio-specific modulator of H-NS function that influences the regulation and acquisition of virulence-defining genetic elements. Knowledge of these interactions sheds light on HNS’ role in defining the virulence potential of V. cholerae and reveals a novel H-NS interactor similar to those present in other Gram-negative bacteria

Elucidating Factors Affecting H-NS-mediated Regulation of Horizontally Acquired Genes in Vibrio Cholerae

Elucidating Factors Affecting H-NS-mediated Regulation of Horizontally Acquired Genes in Vibrio Cholerae PDF Author: Aaron Ross Conrado
Publisher:
ISBN:
Category :
Languages : en
Pages : 198

Book Description
Horizontal gene transfer amongst bacteria plays a critical role in the evolution, emergence, and virulence of both currently recognized and novel pathogens. Vibrio cholerae exemplifies this process, as benign environmental isolates emerge as pandemic pathogens through the acquisition and incorporation of genetic elements encoding virulence factors into their progenitor genomes. In V. cholerae, these genes are localized to distinct areas of the chromosome, known as horizontally acquired islands (HAIs), which are characterized by a lower GC-content than the progenitor genome. In cholera and many other Gram-negative enterics, AT-rich DNA is bound by the H-NS protein immediately upon entrance into the cell, silencing the expression of this potentially toxic DNA. In other enterics, some proteins can remove H-NS from the DNA, allowing the cell to probe these novel genes, while others can interact with H-NS to maintain regulatory control and ensure derepression only happens when appropriate. However, such interactions with H-NS have not been observed in V. cholerae. Here, we discover and characterization of the genetic relationships between H-NS and an H-NS antagonist (ToxR, an essential protein for virulence), as well as an H-NS enhancer (TsrA, a poorly understood protein) in V. cholerae. ToxR is known to be a master activator of virulence, but we demonstrate that ToxR’s critical role is not direct activation, but rather to antagonize H-NS binding at shared binding loci related to host colonization and biofilm formation. Furthermore, TsrA, previously shown to be involved in regulation of type-VI secretion, was detected through immunoprecipitation of H-NS, followed by LC-MS/MS. Subsequent genetic analyses revealed that TsrA enhances H-NS repression of virulence genes on HAIs. Interestingly, TsrA enhances H-NS enrichment at areas of low-GC content, similar to the H-NS interactors in other enterics that V. cholerae was thought to lack. TsrA deletion also affects uptake of a mobile genetic element, establishing the first Vibrio-specific modulator of H-NS function that influences the regulation and acquisition of virulence-defining genetic elements. Knowledge of these interactions sheds light on HNS’ role in defining the virulence potential of V. cholerae and reveals a novel H-NS interactor similar to those present in other Gram-negative bacteria

CRISPR-Cas Systems

CRISPR-Cas Systems PDF Author: Rodolphe Barrangou
Publisher: Springer Science & Business Media
ISBN: 364234657X
Category : Science
Languages : en
Pages : 300

Book Description
CRISPR/Cas is a recently described defense system that protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. A wide spectrum of distinct CRISPR/Cas systems has been identified in at least half of the available prokaryotic genomes. On-going structural and functional analyses have resulted in a far greater insight into the functions and possible applications of these systems, although many secrets remain to be discovered. In this book, experts summarize the state of the art in this exciting field.

Bacterial Chromatin

Bacterial Chromatin PDF Author: Remus T. Dame
Publisher: Springer Nature
ISBN: 1071639307
Category :
Languages : en
Pages : 654

Book Description


The Genus Yersinia:

The Genus Yersinia: PDF Author: Robert D. Perry
Publisher: Springer Science & Business Media
ISBN: 0387721231
Category : Medical
Languages : en
Pages : 454

Book Description
The 9th International Symposium on Yersinia was held in Lexington, Kentucky, USA on October 10-14, 2006. Over 250 Yersinia researchers from 18 countries gathered to present and discuss their research. In addition to 37 oral presentations, there were 150 poster presentations. This Symposium volume is based on selected presentations from the meeting and contains both reviews and research articles. It is divided into six topic areas: 1) genomics; 2) structure and metabolism; 3) regulatory mechanisms; 4) pathogenesis and host interactions; 5) molecular epidemiology and detection; and 6) vaccine and antimicrobial therapy development. Consequently, this volume covers a wide range of current research areas in the Yersinia field.

Metal Transporters

Metal Transporters PDF Author: Jose M. Arguello
Publisher: Academic Press
ISBN: 0123943906
Category : Science
Languages : en
Pages : 478

Book Description
This volume of Current Topics in Membranes focuses on metal transmembrane transporters and pumps, a recently discovered family of membrane proteins with many important roles in the physiology of living organisms. The book summarizes the most recent advances in the field of metal ion transport and provides a broad overview of the major classes of transporters involved in homeostasis of heavy metals. Various families of the transporters and metal specificities are discussed with the focus on the structural and mechanistic aspects of their function and regulation. The reader will access information obtained through a variety of approaches ranging from X-ray crystallography to cell biology and bioinformatics, which have been applied to transporters identified in diverse biological systems, such as pathogenic bacteria, plants, humans and others. Field is cutting-edge and a lot of the information is new to research community Wide breadth of topic coverage Contributors of high renown and expertise

Molecular Basis of Bacterial Pathogenesis

Molecular Basis of Bacterial Pathogenesis PDF Author: Barbara H. Iglewski
Publisher: Elsevier
ISBN: 0323148670
Category : Science
Languages : en
Pages : 486

Book Description
Molecular Basis of Bacterial Pathogenesis focuses on the molecular mechanism of disease associated with bacterial pathogens. Topics covered include the population genetics of bacterial pathogenesis; environmental modulation of gene expression in gram-negative pathogens; and bacterial invasion and intracellular growth. Bacterial toxins are also discussed. This volume is comprised of 20 chapters and begins with an overview of pathogenesis, paying particular attention to common elements and genetic mechanisms of regulation. The discovery that many bacterial pathogens are clonal, with individual clones often having a greater virulence than others, is then considered. The next section deals with the regulation of synthesis of surface components and their role in colonization of the host and/or evasion of the host immune defense systems; antigenic variation and its role in evasion of the host immune response; and the role of iron acquisition systems in the colonization of the host. Subsequent chapters explore the invasion and intracellular growth of facultative and obligate intracellular parasites. The last section is devoted to studies on the role of bacterial toxic products in pathogenesis. Bacterial lipopolysaccharides (endotoxins) and exotoxins are described. This book should be of interest to molecular biologists, physiologists, clinical specialists, pathologists, and geneticists.

Urinary Tract Infections

Urinary Tract Infections PDF Author: Harry L. T. Mobley
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 464

Book Description
This volume offers a comprehensive review of both the basic sciences and the important areas of clinical management pertaining to one of the most common infectious disease problems today. The pioneering work of some of the early molecular biologists is covered in the first part of the book. Part Two goes on to review the major areas of patient care and interesting areas of clinical practice. This book will be a very useful reference resource for all infectious disease physicians and will serve as an important overview of the science for all people working in the field of microbial pathogenesis

Structure and Function of the Bacterial Genome

Structure and Function of the Bacterial Genome PDF Author: Charles J. Dorman
Publisher: John Wiley & Sons
ISBN: 1119308798
Category : Science
Languages : en
Pages : 437

Book Description
Presents an integrated view of the expression of bacterial genetic information, genome architecture and function, and bacterial physiology and pathogenesis This book blends information from the very latest research on bacterial chromosome and nucleoid architecture, whole-genome analysis, cell signaling, and gene expression control with well-known gene regulation paradigms from model organisms (including pathogens) to give readers a picture of how information flows from the environment to the gene, modulating its expression and influencing the competitive fitness of the microbe. Structure and Function of the Bacterial Genome explores the governance of the expression of the genes that make a bacterium what it is, and updates the basics of gene expression control with information about transcription promoter structure and function, the role of DNA as a regulatory factor (in addition to its role as a carrier of genetic information), small RNAs, RNAs that sense chemical signals, ribosomes and translation, posttranslational modification of proteins, and protein secretion. It looks at the forces driving the conservation and the evolution of the dynamic genome and offers chapters that cover DNA replication, DNA repair, plasmid biology, recombination, transposition, the roles of repetitive DNA sequences, horizontal gene transfer, the defense of the genome by CRISPR-Cas, restriction enzymes, Argonaute proteins and BREX systems. The book finishes with a chapter that gives an integrated overview of genome structure and function. Blends knowledge of gene regulatory mechanisms with a consideration of nucleoid structure and dynamics Offers a 'DNA-centric' approach to considering transcription control Views horizontal gene transfer from a gene regulation perspective Assesses the opportunities and limitations of designing synthetic microbes or rewiring existing ones Structure and Function of the Bacterial Genome is an ideal book for graduate and undergraduate students studying microbial cell biology, bacterial pathogenesis, gene regulation, and molecular microbiology. It will also appeal to principal investigators conducting research on these and related topics and researchers in synthetic biology and other arms of biotechnology.

Toxin-Antitoxin Systems in Pathogenic Bacteria

Toxin-Antitoxin Systems in Pathogenic Bacteria PDF Author: Juan Carlos Alonso
Publisher: Mdpi AG
ISBN: 9783036506746
Category : Science
Languages : en
Pages : 170

Book Description
Bacterial toxin-antitoxin (TA) systems, which are ubiquitously present in bacterial genomes, are not essential for normal cell proliferation. The TA systems regulate fundamental cellular processes, facilitate survival under stress conditions, have essential roles in virulence and represent potential therapeutic targets. These genetic TA loci are also shown to be involved in the maintenance of successful multidrug-resistant mobile genetic elements. The TA systems are classified as types I to VI, according to the nature of the antitoxin and to the mode of toxin inhibition. Type II TA systems encode a labile antitoxin and its stable toxin; degradation of the antitoxin renders a free toxin, which is bacteriostatic by nature. A free toxin generates a reversible state with low metabolic activity (quiescence) by affecting important functions of bacterial cells such as transcription, translation, DNA replication, replication and cell-wall synthesis, biofilm formation, phage predation, the regulation of nucleotide pool, etc., whereas antitoxins are toxin inhibitors. Under stress conditions, the TA systems might form networks. To understand the basis of the unique response of TA systems to stress, the prime causes of the emergence of drug-resistant strains, and their contribution to therapy failure and the development of chronic and recurrent infections, must be known in order to grasp how TA systems contribute to the mechanisms of phenotypic heterogeneity and pathogenesis that will enable the rational development of new treatments for infections caused by pathogens.

Regulation of Bacterial Virulence

Regulation of Bacterial Virulence PDF Author: Michael L. Vasil
Publisher: American Society for Microbiology Press
ISBN: 1555816762
Category : Science
Languages : en
Pages : 1189

Book Description
A comprehensive compendium of scholarly contributions relating to bacterial virulence gene regulation. • Provides insights into global control and the switch between distinct infectious states (e.g., acute vs. chronic). • Considers key issues about the mechanisms of gene regulation relating to: surface factors, exported toxins and export mechanisms. • Reflects on how the regulation of intracellular lifestyles and the response to stress can ultimately have an impact on the outcome of an infection. • Highlights and examines some emerging regulatory mechanisms of special significance. • Serves as an ideal compendium of valuable topics for students, researchers and faculty with interests in how the mechanisms of gene regulation ultimately affect the outcome of an array of bacterial infectious diseases.