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Author: Salvador Almagro-Moreno Publisher: ISBN: Category : Bacteriology Languages : en Pages : 187
Book Description
The emergence of many pathogenic species is due to the acquisition of genetic material in the form of pathogenicity islands (PAIs). As a model PAI, we work with Vibrio Pathogenicity Island-2 (VPI-2), a 57 kb integrative element encoded within pathogenic strains of Vibrio cholerae. V. cholerae is a natural inhabitant of brackish and estuarine environments; however it is widely known as the etiological agent of the severe diarrheal disease cholera. A neuraminidase (NanH) is encoded within VPI-2 that unmasks the receptors of the cholera toxin, the main cause of the watery diarrhea. The term sialic acid embraces a diverse group of nine-carbon aminosugars that are widely found in mucous surfaces such as the human gut. In this study, we examined the distribution and evolution of the genes involved in the catabolism of sialic acid among bacteria (Nan) and found that they were confined to pathogenic and commensal organisms. We also uncovered several putative HGT events, some of them among kingdoms. Subsequently, we determined the function of the NanA, NanE and NanK proteins encoded within VPI-2 in V. cholerae. In addition, we found that the ability to utilize sialic acid as a carbon source conferred a competitive advantage to pathogenic isolates of V. cholerae, highlighting an important relationship between the exploitation of host{u2019}s resources and bacterial colonization. Consequently, we focused on the first step in the transfer of virulence genes within a PAI through the study of VPI-2 excision. We found that VPI-2 excision is affected by environmental stimuli. and is tightly regulated by its cognate integrase and two novel RDFs. Interestingly, one of the RDFs also affected the excision of another PAI, showing for the first time cross-talk among two PAIs. We also studied the evolution of VPI-2 among a wide number of sequenced V. cholerae.
Author: Salvador Almagro-Moreno Publisher: ISBN: Category : Bacteriology Languages : en Pages : 187
Book Description
The emergence of many pathogenic species is due to the acquisition of genetic material in the form of pathogenicity islands (PAIs). As a model PAI, we work with Vibrio Pathogenicity Island-2 (VPI-2), a 57 kb integrative element encoded within pathogenic strains of Vibrio cholerae. V. cholerae is a natural inhabitant of brackish and estuarine environments; however it is widely known as the etiological agent of the severe diarrheal disease cholera. A neuraminidase (NanH) is encoded within VPI-2 that unmasks the receptors of the cholera toxin, the main cause of the watery diarrhea. The term sialic acid embraces a diverse group of nine-carbon aminosugars that are widely found in mucous surfaces such as the human gut. In this study, we examined the distribution and evolution of the genes involved in the catabolism of sialic acid among bacteria (Nan) and found that they were confined to pathogenic and commensal organisms. We also uncovered several putative HGT events, some of them among kingdoms. Subsequently, we determined the function of the NanA, NanE and NanK proteins encoded within VPI-2 in V. cholerae. In addition, we found that the ability to utilize sialic acid as a carbon source conferred a competitive advantage to pathogenic isolates of V. cholerae, highlighting an important relationship between the exploitation of host{u2019}s resources and bacterial colonization. Consequently, we focused on the first step in the transfer of virulence genes within a PAI through the study of VPI-2 excision. We found that VPI-2 excision is affected by environmental stimuli. and is tightly regulated by its cognate integrase and two novel RDFs. Interestingly, one of the RDFs also affected the excision of another PAI, showing for the first time cross-talk among two PAIs. We also studied the evolution of VPI-2 among a wide number of sequenced V. cholerae.
Author: William S. Jermyn Publisher: ISBN: Category : Microbiology Languages : en Pages : 177
Book Description
Vibrio cholerae is a Gram negative, curved rod shaped bacterium and is ubiquitous in marine an estuarine environments. V. cholerae is the etiological agent of the profuse, secretory diarrheal disease cholera. Two critical virulence factors, the toxin coregulated pilin (TCP) and cholera toxin (CT) is responsible for the pathogenicity of the bacterium. Both virulence factors are encoded on mobile genetic elements that can be transferred to non-pathogenic strains, enabling these strains to colonise and cause disease. The genes encoding the TCP pilin are located on the Vibrio pathogenicity island; whereas the CT genes are encoded on a filamentous bacteriophage CTX. Neuraminidase is a virulence factor that is thought to act synergistically with CT, by increasing the numbers of receptors available for CT binding. Numerous reports have suggested that neuraminidase is horizontally transferred in bacteria, for example the carriage of the nanH gene on Fels-1 bacteriophage in Salmonella typhimurium LT2. The aim of this thesis was to examine the mechanism of horizontal transfer of nanH in V. cholerae. Molecular and bioinformatics analyses revealed that nanH is encoded on a second pathogenicity island in V. cholerae, which was subsequently named Vibrio pathogenicity island-2 (VPI-2). The island is 57.3 kb in size and consists of three distinct regions; a type-1 restriction modification system, a nan-nag region and a Mu phage-like region. VPI-2 exhibits many of the characteristics of pathogenicity islands such as being located adjacent to a tRNA gene and is found predominantly in pathogenic strains. Interestingly, the island is also prevalent in V. mimicus, a species of Vibrio that is closely related to V. cholerae. The VPI-2 is inserted into the same chromosomal site in both species, adjacent to a tRNA serine and consists of both the nan-nag and Mu phage regions. Intriguingly, the Mu phage region is predominantly associated with clinical isolates whereas the nan-nag region is prevalent in both clinical and environmental isolates. Multi locus sequence analysis indicates that the VPI-2 has recently been transferred between the two species.
Author: Megan R. Carpenter Publisher: ISBN: 9781369351071 Category : Languages : en Pages : 149
Book Description
Pathogenicity islands (PAIs) are mobile integrated genetic elements (MIGEs) that contain a diverse range of virulence factors and are essential in the evolution of pathogenic bacteria. PAIs are widespread among bacteria and integrate into the host genome, commonly at a tRNA locus, via integrase mediated site-specific recombination. The excision of PAIs is the first step in the horizontal transfer of these elements and is not well understood. The work in this dissertation examined the role of recombination directionality factors (RDFs) and their relationship with integrases in the excision of two PAIs essential for Vibrio cholerae host colonization: Vibrio pathogenicity island-1 (VPI-1) and VPI-2. VPI-1 does not contain an RDF, which allowed us to answer the question of whether RDFs are an absolute requirement for excision. We found that an RDF was required for efficient excision of VPI-2 but not VPI-1, and that RDFs can induce excision of both islands. Expression data revealed that the RDFs act as transcriptional repressors to both VPI-1 and VPI-2 encoded integrases. We demonstrated that the RDFs Vibrio excision factor (Vef) A and VefB bind at the attachment sites (overlapping the int promoter region) of VPI-1 and VPI-2, thus supporting this mode of integrase repression. In addition, V. cholerae RDFs are promiscuous due to their dual functions of promoting excision of both VPI-1 and VPI-2 and acting as negative transcriptional regulators of the integrases. This is the first demonstration of cross-talk between PAIs mediated via RDFs which reveals the complex interactions that occur between separately acquired MIGEs. In chapter 3 we identify several islands with novel cargo genes and variant combinations of the VPI recombination modules described in chapter2. An island we named VPI-3 in V. cholerae NRT36S contains a type three secretion system (T3SS) and an island we named VPI-6 in V. cholerae RC385 contains genes encoding for a CRISPR-Cas system and type VI secretion system (T6SS) were examined in this study. We showed that both VPI-3 and VPI-6 can excise from the bacterial chromosome. Evolutionary analysis of these island regions reveals a modular structure indicating that parts of these islands were likely acquired separately. These data demonstrate that identical recombination modules that catalyze integration and excision from the chromosome can acquire diverse cargo genes. In chapter 4 we examine the role of host encoded factors on excision of a filamentous phage named f237, found in the human pathogen Vibrio parahaemolyticus. Here we demonstrate that the quorum sensing regulator luxO is involved in regulating f237 excision and transcription of f237 encoded genes. Specifically, we present evidence for the direct regulation of phage f237 by the high cell density quorum sensing regulator OpaR. In a luxO mutant, cells are locked in a high cell density state and OpaR is constitutively expressed; in this mutant we showed that several f237 genes are more highly expressed, ranging from 3-fold to over 60-fold, relative to wild-type. We found that this increase in expression also correlated with a greater than 20-fold increase in production of f237 phage circular intermediates. Additionally, we found an increase in the amount of the attB excision product in a luxO mutant relative to wild-type. The function of this excision remains unknown and its effects on the physiology of the cell, if any. Given that increased f237 expression and circular intermediate (CI) production were observed in a luxO mutant, we determined whether OpaR may be responsible for these phenotypes. We confirmed that OpaR could bind to these DNA regions using EMSA assays. All these data support the model that OpaR is directly and positively regulating the transcription of f237 genes as well as production of f237 circular intermediates.
Author: Kaye Wachsmuth Publisher: ISBN: Category : Cholera Languages : en Pages : 488
Book Description
Presents the latest molecular studies of virulence, colonization, gene regulation, and the O1 antigen. Gives an in-depth and analytical approach to the epidemiology of cholera that includes outbreak investigations, case-control studies, and surveillance functions. Describes the molecular approach to epidemiologic problems and questions. Tracks the global spread of cholera by genetically defining individual strains. Addresses possible intervention and prevention strategies, including the latest vaccines, and their public health relevance.
Author: Salvador Almagro-Moreno Publisher: Springer Nature ISBN: 3031229975 Category : Science Languages : en Pages : 356
Book Description
This book addresses current topics on pathogenic Vibrio spp. from a comprehensive and holistic perspective. Here, experts in the field provide timely chapters, ranging from genomics, pathogen emergence, and epidemiology to pathogenesis, virulence regulation and host colonization. Questions addressed include: How does climate change affect the spread of these bacteria? What is the status of current vaccines? Are there novel therapeutic options to treat Vibrio infections? Is there likelihood of emergence of new pathogenic strains or species? Can insights from mathematical models and epidemiology lead to prediction of pathogen outbreaks? Recent decades have seen a steady increase in Vibrio spp. infections originating in aquatic and marine habitats, driven by higher human population densities, warming of polluted oceans, natural and human-made disasters, and mass seafood production. These conditions increase the likelihood of pathogenic Vibrio spp. coming into contact with humans, making their study even more timely and relevant as these problems escalate over time. This book is a valuable resource for health management professionals, experienced microbiologists/ microbial ecologists, and early career scientists alike who want to learn more about these important environmental human pathogens. The ideas and technologies presented in this book for preventing, controlling, and monitoring Vibrio spp. infections contribute to the UN Sustainable Development Goal 3: Good Health and Well-Being.
Author: Joseph E. Alouf Publisher: Elsevier ISBN: 0080456987 Category : Science Languages : en Pages : 1072
Book Description
This book describes the major achievements and discoveries relevant to bacterial protein toxins since the turn of the new century illustrated by the discovery of more than fifty novel toxins (many of them identified through genome screening). The establishment of the three-dimensional crystal structure of more than 20 toxins during the same period offers deeper knowledge of structure-activity relationships and provides a framework to understand how toxins recognize receptors, penetrate membranes and interact with and modify intracellular substrates. - Edited by two of the most highly regarded experts in the field from the Institut Pasteur, France - 14 brand new chapters dedicated to coverage of historical and general aspects of toxinology - Includes the major toxins of both basic and clinical interest are described in depth - Details applied aspects of toxins such as therapy, vaccinology, and toolkits in cell biology - Evolutionary and functional aspects of bacterial toxins evaluated and summarized - Toxin applications in cell biology presented - Therapy (cancer therapy, dystonias) discussed - Vaccines (native and genetically engineered vaccines) featured - Toxins discussed as biological weapons, comprising chapters on anthrax, diphtheria, ricin etc.
Author: Salvador Almagro-Moreno
Author: Salvador Almagro-Moreno
Author: William S. Jermyn
Author: Rita R. Colwell
Author: Megan R. Carpenter
Author: Remus T. Dame
Author: Lixing Huang
Author: United States. Food and Drug Administration. Division of Microbiology
Author: Kaye Wachsmuth
Author: Salvador Almagro-Moreno
Author: Joseph E. Alouf