Author: Sinem Beyhan PelvanPublisher:
ISBN:
Category :
Languages : en
Pages : 580
Book Description
C-DI-GMP Signaling in Vibrio Cholerae
Author: Sinem Beyhan PelvanBiofilms and Beyond
Author: Nicolas Luis FernandezPublisher:
ISBN: 9781392517116
Category : Electronic dissertations
Languages : en
Pages : 164
Book Description
The second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) is often utilized by bacteria to transduce external information inside the cell to allow the appropriate response. Soon after investigations began, the connection between c-di-GMP signaling and the transition between sessile and motile lifestyles became clear. Numerous reports demonstrate c-di-GMP promotes production of the biofilm matrix while simultaneously decreasing motility through diverse mechanisms. Researchers also identified c-di-GMP as a signal in other cellular processes in organisms with niche specific phenotypes such as promoting asymmetric cell division, differentiation, predation, and pathogenesis. However, with such vast signaling networks in some bacteria, whether c-di-GMP had a larger influence on controlling cell behavior was to be determined.In this work, I provide examples of how the aquatic organism and human pathogen Vibrio cholerae utilizes c-di-GMP signaling to connect disparate cell behaviors with biofilm formation and explore how these behaviors could promote survival in its natural reservoir. This is exemplified in Chapters 2 and 3, where I demonstrate c-di-GMP increases tolerance to DNA damage and oxidative stress. Importantly, these responses were independent of biofilm matrix production, which can often provide protection from antimicrobials. My data indicate c-di-GMP specifically increases expression of genes involved in DNA repair and antioxidant production, which is sufficient to provide a growth advantage under stressful conditions. Additionally, these responses to increased c-di-GMP were dependent on a c-di-GMP dependent transcription factor, VpsT, which is responsible for biofilm matrix production. Thus, these data support a model where, under high c-di-GMP conditions, matrix production is co-regulated with DNA repair and antioxidant production, suggesting biofilm formation in V. cholerae involves a pre-emptive induction of stress responses, which could promote persistence in the environment.In chapter 4, I uncover an important, previously unrecognized, role for c-di-GMP signaling: control of cell shape to promote biofilm formation. V. cholerae adopts a vibrioid, or curve-rod, appearance which was first observed by early microbiology pioneers in the 1800's. Further examination by Arthur Henrici in 1928 found that V. cholerae shape is heterogenous and was influenced by growth phase. However, how V. cholerae regulated its shape change and the ecological benefits of such changes remained a mystery. In this work, I found that high c-di-GMP concentrations caused the straightening of the vibrioid shape. Disrupting this process by forcing cells to remain curved during surface colonization caused defects in biofilm formation. By using single-cell analysis, my work suggests curvature causes irregularities in cell-to-cell contact during the early stages of biofilm formation. In summation, by orchestrating matrix production, stress responses, and cell shape changes, my results indicate c-di-GMP plays a global role in V. cholerae by preparing cells as they transition to the biofilm lifestyle.
The Second Messenger Cyclic Di-GMP
Author: Alan J. WolfePublisher: American Society for Microbiology Press
ISBN: 1555814999
Category : Science
Languages : en
Pages : 714
Book Description
A comprehensive reference on the state of the science for both experienced researchers and for those who are interested in discovering its many promising applications. • Examines c-di-GMP signaling from a variety of angles, beginning with an introductory chapter that compares c-di-GMP to the better-known second messenger cAMP. • Recounts the discovery of c-di-GMP, explains the important role of bioinformatics in the development and continued evolution of the field, and describes the fundamental structure, function, regulation, and integration of c-di-GMP pathways. • Explores the role of c-di-GMP in such diverse processes as flagellar biogenesis and motility, extracellular polysaccharide biosynthesis, biofilm development, virulence, and innate host immunity.
Environmental Signals and Regulatory Networks Controlling Biofilm Formation and Motility in Vibrio Cholerae
Author: Nicholas J. ShikumaMicrobial Cyclic Di-Nucleotide Signaling
Author: Shan-Ho ChouPublisher: Springer Nature
ISBN: 3030333086
Category : Science
Languages : en
Pages : 640
Book Description
This book explores the broad and diverse biological and physiological impacts of established and newly discovered cyclic di-nucleotide second messenger signaling systems, while also providing descriptions of the intriguing biochemical characteristics of multiple turnover enzymes and receptors. The respective chapters discuss the commonalities and diversity of cyclic di-GMP, cyclic di-AMP and recently discovered cyclic GMP-AMP signaling systems in manifold Gram-negative and Gram-positive bacteria. The global human pathogens Mycobacterium tuberculosis, Vibrio cholerae, Salmonella typhimurium, Escherichia coli and Streptococcus pneumoniae, the facultative human pathogen Pseudomonas aeruginosa, global plant pathogens as exemplified by Xanthomonas campestris and Burkholderia spp., and the omnipresent probiotic Lactobacilli, as well as environmentally important photoautotrophic cyanobacteria, the multicellular Myxococcus xanthus, and chemolithotrophic Acidithiobacillus are among the representatives of the microbial kingdom that are described. In turn, the various aspects of bacterial physiology affected by these signaling systems– e.g. biofilm formation and dispersal, the cell cycle, motility, virulence, production of antimicrobials, fundamental metabolism and osmohomeostasis – are discussed in detail in the context of different microorganisms. Dedicated chapters focus on the population diversity of cyclic dinucleotide signaling systems, their tendency to be horizontally transferred, the cyclic di-GMP signaling system in the social amoeba Dictyostelium, honorary cyclic (di)nucleotides, and the development of strategies for interfering with cyclic dinucleotide signaling in order to manipulate microbial behavior. Taken together, the chapters provide an authoritative source of information for a broad readership: beginners and advanced researchers from various disciplines; individuals seeking a broad overview of cyclic di-nucleotide signaling; and those who want to learn more about specific aspects. Also featuring reviews with a forward-looking perspective, the book offers a valuable source of inspiration for future research directions.
Environmental Regulation of Cyclic Di-GMP Turnover in Vibrio Cholerae
Author: Benjamin J. KoestlerPublisher:
ISBN: 9781303851162
Category : Adenoviruses
Languages : en
Pages : 159
Book Description
To Stick Or Swim
Author: Disha SrivastavaPublisher:
ISBN: 9781303874635
Category : Bacteria
Languages : en
Pages : 195
Book Description
Identification and Structure-function Analyses of Bacterial C-di-GMP Receptors
Author: Petya Violinova KrastevaPublisher:
ISBN:
Category :
Languages : en
Pages : 202
Book Description
In recent years a novel, nucleotide-based small molecule, c-di-GMP, has emerged in the spotlight of scientific investigation as a second messenger unique to the bacterial world. The discovery that its intracellular levels strictly regulate cell adhesion and persistence of bacterial biofilms on one hand, and motility and virulence of planktonic cells on the other, has related this RNA molecule to a variety of disease states including both chronic and acute bacterial infections. Interestingly, intracellular signaling mechanisms involving c-di-GMP appear to be spatially restricted, yet cellular targets for this nucleotide remain mostly unknown. Here we set out to identify and provide comprehensive structure-function analyses of putative or known c-di-GMP receptors. By using structural biology methods we would first determine the atomic resolution structures and conformational states of appropriate targets and then use these molecular blueprints to guide our research into their mechanistic role in the big picture of intracellular signaling networks. We identified VpsT of V.cholerae as a novel c-di-GMP receptor and solved the crystal structures of the nucleotide-free and c-di-GMP-bound states. Our studies identified two biologically relevant dimerization interfaces and the potential formation of higher order oligomeric species assembling upon nucleotide recognition. VpsT defines a novel class of response regulators that utilize a characteristic structural feature to dimerize upon a signaling input regardless of concurrent phosphorylation events. The relative orientation of the DNA-binding domains of VpsT favors a model in which gene regulation is likely accompanied by major changes in DNA architecture. We showed that VpsT is a master regulator of biofilm formation, integrating c-di-GMP signaling events to inversely control exopolysaccharide production and flagellar motility. In a separate study, we provide a complete mechanistic analysis of the structure and function of LapD, a transmembrane c-di-GMP receptor in P. fluorescens which directly translates intracellular c-di-GMP levels in a signal for biofilm dispersal or initiation. We solved three novel crystal structures capturing distinct intermediates in the inside-out signaling process. Most importantly, our structural and functional analyses helped us identify homologous systems in a number of free-living and pathogenic species, likely controlling biofilm formation or toxin expression in a largely similar manner.
Characterization of Cyclic-gmp-amp Signaling and Novel Gene Networks in the Vibrio Seventh Pandemic Islands of El Tor Vibrio Cholerae
Author: Geoffrey Blaine-Graessley SeverinPublisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages : 105
Book Description
Vibrio cholerae is the causative agent of the diarrheal disease cholera, for which there have been seven pandemics. The first six pandemics (1817-1923) have been attributed to strains of the classical biotype while the seventh pandemic (1961- current) is being perpetuated by circulating strains of the El Tor biotype. It is hypothesized that El Tor's acquisition of two unique genomic islands of unknown origins, Vibrio Seventh Pandemic Island 1 & 2 (VSP-1 & 2), potentiated its displacement of classical strains in both environmental and clinical reservoirs prior to the seventh pandemic. Despite their connection to the pandemic evolution of the El Tor biotype and the likelihood they encode a wealth of novel biological functions the majority of the ~ 36 ORFs in the VSP islands have remained uncharacterized. The works presented in the thesis represent examples of our collective efforts to understand the unique traits afforded to the El Tor biotype by the VSP islands. .In 2012, ten years after the initial discovery of the VSP islands, the cyclic di-nucleotide synthase DncV was identified in VSP-1 and shown to synthesize the novel second messenger cyclic-GMP-AMP (cGAMP). Despite this significant discovery, cGAMP remained an orphan second messenger in bacteria for six years. In Chapter 2, I present our identification of the first cGAMP signaling network in bacteria by connecting the synthesis of cGAMP to the allosteric activation of the VSP-1 encoded patatin-like phospholipase vc0178, now named CapV. This finding helped catalyze the revelation that homologous cyclic-dinucleotide signaling networks contribute to bacteriophage-immunity and are distributed widely across the bacterial phyla.dncV and capV represent just two of the ~ 11 ORFs encoded in VSP-1, therefore we hypothesized that cGAMP signaling may extend to include additional genes within the island. Bioinformatic analysis of VSP island genes performed in collaboration with the laboratory of Eva Top at the University of Idaho predicted that dncV was likely to share a biological pathway with the VSP-1 encoded putative deoxycytidylate deaminase vc0175, we have now named DcdV. In Chapter 3, I describe our ongoing efforts to understand the biological function of DcdV and the discovery of its novel negative regulator DifV.The work presented in this thesis has made fundamental contribution to understanding the pandemic evolution of the El Tor biotype and the utility homologous genes afford to their bacterial host while providing a roadmap for further exploration of the biological role of the VSP-1 and VSP-2 islands in pandemic V. cholerae.
Regulation of Bacterial Virulence
Author: Michael L. VasilPublisher: 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.