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Development Of Small Molecule Antibiotics Against A Conserved Rna Gene Regulatory Element In Gram-Positive Bacteria, Ville Yrjö Petteri Väre
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 …
Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte
Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte
Legacy Theses & Dissertations (2009 - 2024)
Transcription termination factor Rho is an essential protein in Escherichia coli and related bacteria. The primary function of Rho is to clear unproductive RNA polymerases from the DNA template to minimize negative effects associated with uncontrolled transcription. Although most of the Rho termination events are constitutive, premature Rho-mediated termination was observed at 3% of all affected transcripts indicating active regulation of Rho activity. In this work, we investigated the regulatory mechanism behind premature Rho-dependent transcription termination in two unrelated genes: suhB and topAI. We show that in both cases transcription is terminated inside the coding gene as a consequence of …
Post-Translational Modifications And Functional Studies Of Dksa In Escherichia Coli, Andrew Charles Isidoridy
Post-Translational Modifications And Functional Studies Of Dksa In Escherichia Coli, Andrew Charles Isidoridy
Legacy Theses & Dissertations (2009 - 2024)
DksA is a bacterial gene regulator that functions synergistically with the stress alarmone ppGpp to mediate the stringent response. DksA also functions independently of ppGpp to regulate transcription of a number of genes. DksA function is dependent on its binding affinity to RNA polymerase and requires specific interactions between RNAP and catalytic amino acids located on the coiled coil tip, D74 and A76. While much of the previous work on DksA has focused on understanding the mechanisms of action and the numerous gene targets for transcriptional regulation, little is known about the mechanisms by which DksA expression and function may …
Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods
Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods
Legacy Theses & Dissertations (2009 - 2024)
DksA is a global transcription factor that binds RNAP directly to regulate the expression of many genes and operons, including ribosomal RNA, in a ppGpp-dependent or ppGpp–independent manner. It is also involved in facilitating the process of DNA replication by removing stalled transcription elongation complexes that could block the progress of the replication fork. In addition, DksA is important for colonization, establishment of biofilms, and pathogenesis. In order to sustain these various functions, an adequate level of cellular DksA is required. This work tested the hypothesis that the E. coli dksA is substantially regulated at the level of transcription. Using …
Structural And Functional Characterization Of An Unusual Camp Responsive Transcription Factor, Cmr, In Tb Complex Mycobacteria, Sridevi Ranganathan
Structural And Functional Characterization Of An Unusual Camp Responsive Transcription Factor, Cmr, In Tb Complex Mycobacteria, Sridevi Ranganathan
Legacy Theses & Dissertations (2009 - 2024)
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans, is an intracellular pathogen that infects millions of people every year. Mtb can survive inside the host for extended periods of time by sensing and adapting to the host environmental stressors. Transcriptional gene regulation plays a critical role in this adaptation. This dissertation focuses on understanding the structural and functional aspects of one such transcriptional regulatory unit, Cmr (Rv1675c), in Mtb.