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Regulation Of Acetyl Phosphate-Dependent Acetylation And Identification Of Novel Lysine Acetyltransferases In Escherichia Coli, David George Christensen
Regulation Of Acetyl Phosphate-Dependent Acetylation And Identification Of Novel Lysine Acetyltransferases In Escherichia Coli, David George Christensen
Dissertations
Over billions of years, organisms have organized chemical reactions into metabolic pathways to sustain life. However, metabolic substrates can undergo many uncatalyzed, extra-metabolic reactions. Acetyl phosphate (AcP), an intermediate of the acetate fermentation pathway in E. coli, is one such metabolite that has been shown to non-enzymatically acetylate hundreds of proteins. This diverse set of targets suggests that acetylation could be a way for the cell to sense its nutritional status and regulate protein activity accordingly. However, how E. coli regulates acetylation, if at all, is unknown.Previous work showed that acetylation becomes pronounced in stationary phase cells. I determined that …
Membrane Microdomains As Platforms For Extra-Cellular Fusions, Michael Hantak
Membrane Microdomains As Platforms For Extra-Cellular Fusions, Michael Hantak
Dissertations
Life requires biological membranes. Membrane-enclosed compartments separate and unite through dynamic fission and fusion reactions. These are catalyzed processes that are central in organismal biogenesis. This dissertation focuses on extracellular membrane fusions, which are central to several processes. (1) Enveloped viruses enter cells through membrane fusions. (2) Extracellular vesicles (EVs) also deliver molecules into cells through membrane fusions. (3) Entire cells also fuse together, generating fertilized zygotes, skeletal muscles, and giant cell macrophages.Mechanisms of extracellular membrane fusion are poorly understood. This dissertation aimed to further define these mechanisms. We focused on regulatory cofactors, including tetraspanins, transmembrane proteins that cluster into …
Staphylococcus Aureus Evasion Of The Innate Immune System, James Paul Grayczyk
Staphylococcus Aureus Evasion Of The Innate Immune System, James Paul Grayczyk
Dissertations
Upon entry into the host, pathogens must overcome innate immunity in order to cause disease. The innate immune system represents a fast-acting initial line of defense to prevent infection. In order to withstand innate defenses, bacterial pathogens like the Gram-positive bacterium Staphylococcus aureus, produce a wide array of virulence factors that can inhibit innate immune cell recruitment and antimicrobial activity, or directly target and kill phagocytic leukocytes thereby facilitating pathogenesis. Infection with S. aureus can cause disease in virtually any tissue site and is a significant burden to human health. In this dissertation, we sought to understand how S. aureus …
Aerococcus Urinae: Establishing The Pathogenesis Of An Emerging Uropathogen, Evann E. Hilt
Aerococcus Urinae: Establishing The Pathogenesis Of An Emerging Uropathogen, Evann E. Hilt
Dissertations
Urinary tract infection (UTI) is the world's most common bacterial infection. Much is known about the infectious process (pathogenesis) of a few of the bacteria that cause these infections, especially E. coli. Unfortunately, the pathogenesis of E. coli and other uropathogenic bacteria was explored almost exclusively in the belief that the bladder is supposed to be sterile. Our recent evidence, however, debunks this dogma. We used modern methods to reveal diverse bacterial communities in the bladders of adult women. These communities differ in women with and without lower urinary tract symptoms (LUTS), including UTI and urinary incontinence (UI). Many bacteria …
Assessing The Temporal Dynamics Of The Lower Urinary Tract Microbiota And The Effects Of Lifestyle, Travis Kyle Price
Assessing The Temporal Dynamics Of The Lower Urinary Tract Microbiota And The Effects Of Lifestyle, Travis Kyle Price
Dissertations
Urinary tract infections (UTIs) are among the most common bacterial infections in humans, accounting for $3.5 billion in health care expenditures yearly in the United States alone. Yet, treatments for UTI have seen little innovation over the past decade. As demonstrated in other body sites, such as the vagina and gastrointestinal (GI) tract, acute and infectious diseases often have indirect microbial contributions which serve as intriguing new targets for therapies. The recent discovery of the existence of a resident community of bacteria (i.e., microbiota) in the bladders of both women and men, represents a novel avenue for targeting UTIs. However, …
Generating Biologic And Genetic Research Tools To Investigate Serotype I Feline Coronaviruses, Robert Christian Mettelman
Generating Biologic And Genetic Research Tools To Investigate Serotype I Feline Coronaviruses, Robert Christian Mettelman
Dissertations
Serotype I feline infectious peritonitis virus (FIPV) is an alphacoronavirus of high veterinary importance due to the 99% mortality rate observed in cats. Since the 1980s, robust experimentation on these viruses has been limited by availability of culturable pathogenic strains, few permissive cell lines, and a lack of standardized methods to study their basic virology. These complications have resulted in variable and conflicting literature reports, have slowed study of clinical strains and hindered effective vaccine design. The goal of this dissertation was to develop a laboratory "toolbox" containing standardized methods, permissive cell lines and genetic techniques to alleviate some of …