Microbiology Commons^™

Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez

Dissertations & Theses (Open Access)

Accurate disulfide bond formation is important for proper folding, stability and function of exported proteins. The process of disulfide bond formation, termed oxidative protein folding, is catalyzed by thiol-disulfide oxidoreductase enzymes. Oxidative protein folding pathways influence processes essential for bacterial physiology and pathogenicity. In the Gram-positive actinobacterial pathogens Actinomyces oris and Corynebacterium diphtheriae oxidative protein folding is catalyzed by the primary thiol-disulfide oxidoreductase MdbA. MdbA is required for assembly of adhesive pilus, which mediate receptor-dependent bacterial interactions, or coaggregation, in A. oris. In the first part of this dissertation, I identify components of the electron transport chain (ETC) required for …

Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely

Dissertations & Theses (Open Access)

Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …

Assembly And Display Of Surface Proteins In Actinomyces Oris, Sara Siegel

Dissertations & Theses (Open Access)

Bacteria are an integral part of human health and disease. In the human host, dental plaques form as a result of up to 700 individual bacterial species colonizing oral surfaces and forming a multispecies biofilm. These biofilms are the cause of prevalent human diseases such as dental caries, gingivitis, and periodontitis. The microbes present in the oral biofilm are highly spatially and temporally structured and require a primary colonizing species to adhere to host tissue. As an important primary colonizer of the oral biofilm, the actinobacterium Actinomyces oris utilizes cell wall anchored proteins and glycoconjugates to initiate adherence to host …

Investigating The Single Cell Heterogeneity And Physiological Impact Of Mistranslation, Christopher Evans

Dissertations & Theses (Open Access)

Bacterial populations grow clonal populations; however, individual cells have a variety of phenotypes. The physiological heterogeneity observed in populations has been attributed to variations in the processes of gene expression. For example, promoter expression has been shown to be heterogeneous within a population and contribute to increased stress tolerance in a subpopulation of cells. In comparison to transcription, the influence of translation on single cells is unclear. In this study, my collaborators and I have developed a dual-fluorescence reporter that allows us to measure the mistranslation rate in single cells in vivo. Using this reporter, we found that mistranslation …

Mechanism Of Incorporation And Repair Of Uracil At Highly Transcribed Genes In Saccharomyces Cerevisiae, Norah Auma Owiti

Dissertations & Theses (Open Access)

Recombination and mutagenesis are elevated by high levels of transcription. The correlation between transcription and genome instability is largely explained by the topological and structural changes in DNA and the associated physical obstacles generated by the transcription machinery. However, such explanation does not directly account for the unique types of mutations originating from the non-canonical residues such as uracil, which are also elevated at highly transcribed regions. Apurinic/Apyrimic or Abasic (AP) sites derived from uracil excision, accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) …

Characterization Of Metronidazole- And Vancomycin-Resistant Clinical Isolates Of Clostridium Difficile, Chioma Odo

Dissertations & Theses (Open Access)

Characterization of Metronidazole- and Vancomycin-Resistant Clinical Isolates of Clostridium difficile

Chioma Odo, MS.

Supervisory Professor: Charles Darkoh, Ph.D.

ABSTRACT

The incidence of C. difficile infections (CDI) has been increasing at an alarming rate. This was precipitated by the emergence of strains with increased virulence, disease severity, and high recurrence rates. These strains also exhibit high propensity for resistance to antibiotics such as fluoroquinolones and beta lactams, which has made the treatment of CDI very challenging. Currently, metronidazole and vancomycin are the most commonly used drugs for the treatment of primary CDI. Metronidazole is used for the treatment of mild to …

Functional Similarity Of Prd-Containing Virulence Regulators In Bacillus Anthracis, Malik Raynor

Dissertations & Theses (Open Access)

Bacillus anthracis produces three regulators, AtxA, AcpA, and AcpB, that control virulence gene expression and are members of an emerging class of regulators termed “PCVRs” (Phosphoenolpyruvate-dependent phosphotransferase regulation Domain-Containing Virulence Regulators). AtxA controls expression of the toxin genes; lef, cya, and pag, and is the master virulence regulator and archetype PCVR. AcpA and AcpB are less well studied. AcpA and AcpB independently positively control transcription of the capsule biosynthetic operon capBCADE, and culture conditions that enhance AtxA activity result in capBCADE transcription in strains lacking acpA and acpB. RNA-Seq was used to assess the regulons of the …

Evolution Via Gene Duplication And Alternative Splicing In The Eukaryotic Ski7 And Hbs1 Genes, Alexandra Marshall

Dissertations & Theses (Open Access)

Gene duplication and alternative splicing are both recognized as important drivers of proteomic diversity and innovation during evolution, but the evolutionary changes over long periods of time or the interrelations of the two processes has not been extensively studied. Here I study these phenomena for the SKI7 and HBS1 gene pair. These Saccharomyces cerevisiae genes were created as part of a whole genome duplication (WGD) event and have since functionally diverged. Although both genes function in mRNA surveillance pathways, the two genes act on different RNAs and have different effects on the target mRNAs. Ski7 brings the Ski complex and …