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Full-Text Articles in Microbiology

The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett Dec 2019

The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett

Dissertations

Histoplasma capsulatum(Hc)is a systemic, dimorphic fungal pathogen that affects upwards of 500,000 individuals in the United States annually. Hc grows as a multicellular mold at environmental temperatures; whereas, upon inhalation into a human or other mammalian host, it transforms into a unicellular, pathogenic yeast. The research presented in this dissertation is focused on characterizing the DNA damage-responsive gene HcDDR48. HcDDR48was originally isolated via a subtractive DNA library enriched for transcripts enriched in the mold-phase of Hcgrowth. Upon further analysis we found that HcDDR48is not just expressed in the mold morphotype, but both growth programs …


The Antimicrobial Activity And Cellular Targets Of Plant Derived Aldehydes And Degradable Pro-Antimicrobial Networks In Pseudomonas Aeruginosa, Yetunde Adewunmi Dec 2019

The Antimicrobial Activity And Cellular Targets Of Plant Derived Aldehydes And Degradable Pro-Antimicrobial Networks In Pseudomonas Aeruginosa, Yetunde Adewunmi

Dissertations

Essential oils (EOs) are plant-derived products that have been long exploited for their antimicrobial activities in medicine, agriculture, and food preservation. EOs represent a promising alternative to conventional antibiotics due to the broad-range antimicrobial activity, low toxicity to human commensal bacteria, and the capacity to kill microorganisms without promoting resistance. Despite the progress in the understanding of the biological activity of EOs, many aspects of their mode of action remain inconclusive. The overarching aim of this work was to address these gaps by studying molecular interactions between antimicrobial plant aldehydes and the opportunistic human pathogen Pseudomonas aeruginosa. We initiated …


The Role Of Multidrug Resistance Regulators Mara, Soxs, Rob And Rama In Regulating Virulence Traits In Salmonella Enterica, Srinivas Thota Nov 2019

The Role Of Multidrug Resistance Regulators Mara, Soxs, Rob And Rama In Regulating Virulence Traits In Salmonella Enterica, Srinivas Thota

Dissertations

Enteric pathogens sense numerous signals specific to the anatomical location in the intestine and integrate them with the complex regulatory networks to temporally and spatially regulate their virulence genes. MarA, SoxS, Rob and RamA are homologous transcription factors that belong to AraC family of proteins in Salmonella enterica that primarily were thought to be involved in rendering antibiotic resistance to bacteria by up regulating efflux pumps and down regulating outer membrane porins. The fact that these transcription factors respond to the same intestinal compounds that regulate virulence genes in Salmonella motivated us to look for other roles of these transcription …


Regulation Of Acetyl Phosphate-Dependent Acetylation And Identification Of Novel Lysine Acetyltransferases In Escherichia Coli, David George Christensen Jan 2019

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 Jan 2019

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 Jan 2019

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 Jan 2019

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 Jan 2019

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 Jan 2019

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 …