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University of Tennessee Health Science Center

Medical Biochemistry

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Full-Text Articles in Bacterial Infections and Mycoses

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita Dec 2022

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

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Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette Oct 2020

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

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Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley May 2018

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

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Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo Dec 2015

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

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A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim Dec 2013

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

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Interactions Of Francisella Tularensis With Components Of The Host Fibrinolytic System, Shawn Russell Clinton Dec 2010

Interactions Of Francisella Tularensis With Components Of The Host Fibrinolytic System, Shawn Russell Clinton

Theses and Dissertations (ETD)

Francisella tularensis (FT) is a Gram-negative coccobacillus and causative agent of a life-threatening disease commonly referred to as tularemia. Due to the highly infectious nature of the organism, its previous development as a biowarfare agent and its potential use in acts of bioterrorism, this bacterium is listed as a Category A select agent by the Centers for Disease Control and Prevention (CDC). Efforts to understand the pathogenic mechanisms of FT within the host environment are vital for the development of safe and effective vaccines, as well as treatments, against tularemia. Though considered an intracellular pathogen, FT research of late has …

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