자료유형  

 학위논문

Control Number  

0016934485

International Standard Book Number  

9798380481137

Dewey Decimal Classification Number  

632

Main Entry-Personal Name  

Diaz, Oscar Ramon.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(115 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-04, Section: B.

General Note  

Advisor: Monack, Denise.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Pathogenic bacteria can cause a wide range of diseases, and the factors contributing to the variations in disease outcomes include pathogenicity-associated genetic elements, transcriptional responses, and proteomic composition. Salmonella enterica subspecies enterica is comprised of 2,500 Salmonella serotypes that vary widely in terms of virulence, host range, and geographic distribution. Of these S. enterica subsp. entericaserovars, common serovars associated with human disease include serovars Newport, Typhi, Enteritidis, and Typhimurium. Understanding the determinants of their diversity in bacterial-derived disease would reveal strategies for reducing the health impact of these pathogens.The objective of this work is to profile the transcriptome of Salmonella enterica serovar Typhimurium (S. Typhimurium) during RAW 246.7 macrophage infection and identify the molecular determinants of S. Typhimurium pathogenicity. The transcriptome of S. Typhimurium dynamically responds to the rapid environmental changes intrinsic to its lifestyle, such as entry into the Salmonella containing vacuole (SCV) within macrophages. Intracellular S. Typhimurium must respond to the acidity of the SCV, accumulation of reactive oxygen/nitrogen species, and fluctuations in nutrient availability. In Chapter 1, we describe what is known on S. Typhimurium pathogenicity during human infection and previous molecular approaches for profiling the genetic and transcriptomic determinants of disease.Chapter 2 introduces my novel approach for profiling the transcriptome of intracellularS. Typhimurium during macrophage infection using a comprehensive library of GFP-reporter strains representing ~3,000 computationally identified S. Typhimurium promoters. To begin, we describe in silico and in vitro construction of the S. Typhimurium GFP-reporter library to study the dynamics of transcriptional regulation. Our approach for using time-lapse fluorescence microscopy to comprehensively profile intracellular promoter activity is introduced, as are the methods for quality control of the library. Chapter 2 also provides an overview of the dynamic promoter activity of S. Typhimurium during intracellular infection of RAW 246.7 macrophages. Using bulk measurements and single-cell imaging, we uncover macrophage-specific transcriptional regulation of virulence-related promoters, and previously unidentified transcriptional activity of metabolic genes, prophage genes, and canonical pathogenicity islands during infection. In Chapter 3, we describe the metabolic response of intracellular S. Typhimurium during latestage macrophage infection, specifically, increased activity of promoters-associated with the Entner-Doudoroff pathway. In addition, we provide a brief description of the interserovar variability of pathogenicity-related promoters, thus revealing the influence of transcriptional dynamics in determining serovar-specific regulation of pathogenicityassociated genetic elements. Finally, Chapter 4 discusses the how this dataset should collectively provide a powerful resource for systems-level quantification of Salmonella transcriptional dynamics and integration with an in vitro dataset profiling the S. Typhimurium GFP-reporter library in defined and complex media conditions.

Subject Added Entry-Topical Term  

Prokaryotes.

Subject Added Entry-Topical Term  

Infections.

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Pathogens.

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Salmonella.

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Biofilms.

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Epidemiology.

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Biochemistry.

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Bacteria.

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Biology.

Subject Added Entry-Topical Term  

Metabolism.

Subject Added Entry-Topical Term  

Genomics.

Subject Added Entry-Topical Term  

Gene loci.

Subject Added Entry-Topical Term  

Drug resistance.

Subject Added Entry-Topical Term  

Oxidative stress.

Subject Added Entry-Topical Term  

Plasmids.

Subject Added Entry-Topical Term  

Signal transduction.

Subject Added Entry-Topical Term  

Cells.

Subject Added Entry-Topical Term  

Antibiotics.

Subject Added Entry-Topical Term  

Bacterial infections.

Subject Added Entry-Topical Term  

Genetic engineering.

Subject Added Entry-Topical Term  

Pathogenesis.

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Bioengineering.

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Genetics.

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Pathology.

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Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Pharmacology.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 85-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:642161