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Molecular Mechanisms Shaping Host Range Of A Vector-Borne Pathogen, Thomas Macgregor Hart Jan 2020

Molecular Mechanisms Shaping Host Range Of A Vector-Borne Pathogen, Thomas Macgregor Hart

Legacy Theses & Dissertations (2009 - 2024)

Vector-borne diseases, such as Lyme disease caused by Borrelia burgdorferi sensu lato (Bbsl), have narrow host ranges and are apt models to study host-microparasite coevolution. Some species and strains of Lyme borreliae (LB) are specialists, infecting only mammalian or only avian hosts (ex. Borrelia afzelii and B. garinii, respectively), while others are generalists and infect both hosts (ex. B. burgdorferi). Such host tropisms are hypothesized to be partially shaped by the ability of these pathogens evade host immune defenses, such as complement. Complement is a first line host defense against invading pathogens that kills LB in vitro and inhibits spirochete …


Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller Jan 2020

Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller

Legacy Theses & Dissertations (2009 - 2024)

Translation is a crucial mechanism for generating proteins to carry out cellular processes and for ensuring proper cell functions. Ribosomes are at the center of translation and are complex pieces of machinery. They consist of at least 80 core eukaryotic ribosomal proteins, which are conserved from prokaryotes, and four ribosomal RNAs (rRNAs): 18S, 28S, 5,8A 5S. In addition, numerous translation factors aid the ribosome in protein production. While ribosomes are typically described by these core features, they are known to exist in a heterogenous pool with variations in protein composition, modifications of rRNA, and an assortment of non-ribosomal proteins that …


Development Of Small Molecule Antibiotics Against A Conserved Rna Gene Regulatory Element In Gram-Positive Bacteria, Ville Yrjö Petteri Väre Jan 2020

Development Of Small Molecule Antibiotics Against A Conserved Rna Gene Regulatory Element In Gram-Positive Bacteria, Ville Yrjö Petteri Väre

Legacy Theses & Dissertations (2009 - 2024)

Bacterial infections and the rise of antibiotic resistance, especially multidrug resistant strains, have generated a clear need for discovery of novel therapeutics. Most antibiotics in use today are derivatives of previous antibiotics to which resistance mechanisms already exist, and traditionally they have a single target: either a protein or rRNA. Gram-positive bacteria regulate the expression of several essential genes or operons using a mechanism called the T-box. The T-box is a structurally conserved riboswitch-like gene regulator in the 5’-untranslated region (UTR) of numerous essential genes of Gram-positive bacteria. T-boxes are stabilized by cognate, unacylated tRNA ligands, allowing the formation of …


Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova Jan 2020

Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova

Legacy Theses & Dissertations (2009 - 2024)

The outer membrane (OM) of Gram-negative enteric pathogens like Vibrio cholerae is a barrier against host defense factors, as well as a sensor of physical and chemical stimuli that the bacteria encounter in the gastrointestinal tract. The OM is also the primary target of the mucosal immune response, which consists of secretory antibodies primarily directed against lipopolysaccharide (LPS). ZAC-3 is a monoclonal antibody (MAb) that targets the conserved core/lipid A region of LPS of the pandemic V. cholerae O1 serotype. In a neonatal mouse model, passively administered ZAC-3 IgG has been shown to reduce the ability of V. cholerae to …