Organisms Commons^™

Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest

Theses and Dissertations (ETD)

While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. …

Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland

Theses and Dissertations (ETD)

As a species, humans have become ever reliant on the use of antibiotics to facilitate our everyday lives. The widespread emergence of resistance to currently used antibiotics is commonly attributed to an over use in our society. Such resistance, coupled with a lack of innovation and production of novel antibiotic drugs, threatens to return humanity to an era similar to one before the discovery of the first antibiotics. The need to find new agents to be used in this fight is paramount, as well as learning from our recent failures to produce such compounds. This document will highlight my efforts …

Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard

Theses and Dissertations (ETD)

A novel orthomyxovirus was recently identified from pigs, with subsequent work suggesting the natural reservoir being bovine populations. The virus had genome characteristics most similar to influenza C viruses (ICV) but, due to the extent of sequence divergence, was proposed as a new genus, influenza D virus (IDV). Current literature on IDV has largely focused on the agricultural significance of the virus and provided evidence for the agricultural impact via observation of widespread prevalence and pathology in laboratory infected cattle. However, only one study, which identified 1.3% seroprevalence in a small cohort, has addressed the zoonotic potential of IDV to …

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 …

Genetic Control Of Survival And Weight Loss During Pneumonic Burkholderia Pseudomallei (Bp) Infection, Felicia D. Emery

Theses and Dissertations (ETD)

Burkholderia pseudomallei (Bp) is a saprophytic, gram-negative aerobe and the causative agent of the disease melioidosis. Melioidosis is an infectious disease that occurs in humans and animals and is prevalent in Southeast Asia, northern Australia and other tropical areas. Transmission occurs through direct contact with the organism via ingestion, inhalation, or through open wounds and skin abrasions. Clinical presentation is extremely variable and can range from acute septicemia with bacterial dissemination to distant sites, to an isolated pulmonary infection. Treatment of melioidosis can be problematic because it is often difficult to diagnose and Bp is resistant to a diverse group …

Development And Characterization Of A Recombinant Vesicular Stomatitis Virus (Rvsv) For The Treatment Of Glioblastoma, Erika A. Dillard

Theses and Dissertations (ETD)

Background: Over the past 30 years, little has changed in the treatment modalities and prognosis of patients suffering from Glioblastoma multiforme (GBM), the most common and by far the most devastating adult primary malignant brain tumor. Conventional therapies provide only a marginal increase in survival of GBM patients, post-diagnosis. Therefore, more novel means of treating GBM are needed to increase long-term survival and quality of life for those affected. Replication competent oncolytic viruses (OVs) have recently emerged as a possible option for treatment of high-grade gliomas. Particularly, recombinant vesicular stomatitis virus (rVSV), an enveloped, negative strand RNA virus, has shown …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek

Theses and Dissertations (ETD)

Candida albicans is the most prevalent human fungal pathogen, found as a commensal organism in the mucosa, gastrointestinal, and urogenital tracts of humans. This pathogenic fungus causes a wide spectrum of diseases, including the mucosal infection oropharyngeal candidiasis (OPC) which frequently effects patients with human immunodeficiency virus (HIV). The azole antifungals (such as fluconazole) are the most widely used and important ergosterol biosynthesis inhibitors (EBIs) for the treatment of Candida infections, including OPC. However, the azoles are fungistatic against C. albicans and therefore have limited efficacy against this organism, especially for immunocompromised patients. In C. albicans, the transcription factor Upc2 …

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 …

Transcriptional Regulation Of Azole Antifungal Resistance And Tolerance In Candida Glabrata, Kelly E. Caudle

Theses and Dissertations (ETD)

Azole antifungal resistance has emerged as a significant problem in the management of infections caused by fungi including Candida species. In recent years, Candida glabrata has become the second most common cause of mucosal and invasive fungal infections in humans second to Candida albicans. Not only are systemic C. glabrata infections characterized by high mortality rates, treatment failures to the azole class of antifungals, the most widely used antifungal for treatment of Candida infections, have been reported. Contributing to this problem, C. glabrata exhibits intrinsic reduced susceptibility to the azole antifungals, and the development of high-level azole resistance …

Contribution Of The Membrane-Proximal Region Of The Vesicular Stomatitis Virus Glycoprotein To Host Cell Entry And Membrane Fusion, Elizabeth Lane Matheny

Theses and Dissertations (ETD)

Vesicular stomatitis virus (VSV) is an enveloped, nonsegmented, negative-sense, RNA virus belonging to the Rhabdoviridae family. VSV is considered the prototypic Rhabdovirus due to its simple genetic organization, broad host cell tropism, and ability to be easily grown in cell culture. Therefore, VSV has been used as the prototype to study viral entry, transcription, replication, and assembly. Viral entry, a critical step in the lifecycle of the virus, is mediated by the outer surface protein, G and will be the focus of this dissertation.

We hypothesize that the highly conserved residues in the membrane-proximal region of VSV G protein are …

Studies Of Entry, Reverse Transcription, And Regulation Of Splicing In Retroviruses, Timothy A. Sullivan

Theses and Dissertations (ETD)

The study of retroviruses and their lifecycle has contributed immensely to our knowledge of the world of biology and medicine. The central dogma of the basic flow of genetic information was shattered when the discovery that retroviruses copy their RNA genome into DNA was made. The same enzyme that performs this step, reverse transcriptase (RT), also revolutionized molecular biology when it was used as a tool to generate full length cDNA clones of expressed genes. The impact of retroviruses on the medical field has been extremely exciting as the ideas of using retroviral vectors to deliver genes providing long term …

Investigation Of The Vesicular Stomatitis Virus Matrix Protein: Uncoating And Assembly, Chad E. Mire

Theses and Dissertations (ETD)

Vesicular Stomatitis Virus (VSV) is a simple, enveloped, nonsegmented negative-strand RNA virus and is the prototype rhabdovirus to study viral entry, transcription, replication, and assembly. The matrix protein (M) of VSV is a central component of the viral replication cycle. While being the smallest of the viral proteins it is multifunctional and is involved in uncoating, cytopathic effects (CPE), and assembly of the virus. M protein interactions involved in the uncoating and assembly of VSV have been examined in this dissertation.

Uncoating of VSV involves dissociation of M from the ribonucleoprotein core (RNPs) of the virus. Current models of VSV …

Manipulation Of The Moloney Murine Leukemia Virus Envelope Protein In An Effort To Develop Directly And Indirectly Targeted Retroviral Vectors For Use In Human Gene Therapy, Geneva M. Vasser

Theses and Dissertations (ETD)

Highly effective, targeted therapies against cancer would revolutionize the way people recover from this devastating illness. Gone would be the lingering side effects of the current non-specific treatments and in their place would be faster recovery times, better quality of life both during and after treatment, and less ambiguity about whether or not treatment was effective. This concept will elude modern medicine until treatments can be tailored to the patient's individual and unique disease. This concept of a transient, targeted, and tailored vehicle aimed at cancer cells lends itself to the use of replication deficient retroviral gene therapy vectors with …

Transcriptional Regulation Of Azole Antifungal Resistance In Candida Albicans, Teresa T. Liu

Theses and Dissertations (ETD)

Candida albicans is a pathogenic fungi found in the mucosa, gastrointestinal, and urogenital tracts of humans. Oropharyngeal candidiasis (OPC), an opportunistic mucosal infection caused by C. albicans, occurs most frequently in patients infected with human immunodeficiency virus (HIV). OPC is usually treated with azole antifungals, a class of antifungals that target ergosterol biosynthesis, at low doses over long periods of time. This course of treatment allows for the development of azole resistance.

Two major mechanisms of azole resistance exist in C. albicans, the up-regulation of genes encoding efflux pumps and the up-regulation of ERG11, a gene encoding the azole drug …

Biochemical And Immunological Mechanisms Underlying Differential Interaction Of Superantigens With Host Immunogenetic Factors In Streptococcal Sepsis, Mohammed Nooh

Theses and Dissertations (ETD)

Group A streptococci (GAS) are serious human pathogens that can cause a wide array of diseases ranging from pharyngitis to streptococcal toxic shock (STSS), which is caused by excessive cytokines responses triggered by streptococcal superantigens (Strep SAgs). SAgs interact simultaneously with HLA class II molecules on antigen presenting cells (APC) and with the T cell receptor beta chain variable elements (TCR V) and cause excessive stimulation of both cell types and massive release of inflammatory mediators.

The Strep SAgs include the streptococcal pyrogenic exotoxins (Spes), which play a crucial role in the pathogenesis of severe invasive streptococcal diseases, including Strep …