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Life Sciences

Washington University in St. Louis

Theses/Dissertations

Antibiotic resistance

Publication Year

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Rna Polymerase Binding Protein A (Rbpa) Regulation Of Mycobacteria Transcription And Sensitivity To Fidaxomicin, Jerome Prusa Aug 2021

Rna Polymerase Binding Protein A (Rbpa) Regulation Of Mycobacteria Transcription And Sensitivity To Fidaxomicin, Jerome Prusa

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis is the causative agent of the disease tuberculosis (TB) and remains one of the deadliest microorganisms on the planet. The effort to eradicate M. tuberculosis would benefit from the development of novel therapeutics, which requires a detailed understanding of M. tuberculosis physiology. Like all living organisms, M. tuberculosis gene expression requires transcription. Transcription in the phylum Actinobacteria, which includes mycobacteria, is unique because it includes RNA Polymerase Binding Protein A (RbpA) that is essential in both M. tuberculosis and the nonpathogenic model organism Mycobacterium smegmatis. RbpA increases the housekeeping A and housekeeping like B interactions with the RNA …


Gut Reactions: Quantitative Predictions Of The Responses Of Human Gut Microbiota To Medical Interventions, Amy Elizabeth Langdon May 2021

Gut Reactions: Quantitative Predictions Of The Responses Of Human Gut Microbiota To Medical Interventions, Amy Elizabeth Langdon

Arts & Sciences Electronic Theses and Dissertations

The collection of microbes known as the human microbiome perform vital functions for their host, and when this community becomes unhealthy, its dysbiosis is implicated in a myriad of diseases. The gut microbiota in particular are known to suppress colonization of opportunistic pathogens, regulate the immune system, aid in nutrient breakdown, produce vitamins, and a growing number of other functions. In order to intervene in a dysbiotic microbial ecology, we can try to remove unwanted microbes or try to recolonize the gut with microbes expected to be beneficial. This dissertation provides an overview of the state of medical interventions for …


Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani Jan 2021

Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani

Arts & Sciences Electronic Theses and Dissertations

Complex microbial communities are at the interface of human, animal and environment interconnected ecosystem, where they can move within and between these entities. These microbial communities are mostly beneficial, maintaining the host health and homeostatic state. However, these communities can also serve as reservoirs of antibiotic resistance (AR) genes that may disseminate to pathogen bacteria, compromising the treatment options. Like other microbial communities, human gut microbiome is highly dynamic and can get acutely perturbed with the changes in the habitat, diet, lifestyle and disease. A perturbed gut community structure has profound impact on the host health and physiology. Use of …


Multi-Omic Understanding Of The Evolution Of Xenobiotic Tolerance In Bacterial Isolates And Communities, Tayte Paul Campbell Aug 2019

Multi-Omic Understanding Of The Evolution Of Xenobiotic Tolerance In Bacterial Isolates And Communities, Tayte Paul Campbell

Arts & Sciences Electronic Theses and Dissertations

Xenobiotic compounds are any chemicals that are released into an environment by human action and that occur at concentrations higher than found naturally. Xenobiotics, including aromatic compounds and antibiotics, are recalcitrant to degradation because they are often toxic or mutagenic. Despite this toxicity, bacteria account for a large portion of xenobiotic degradation in the environment. Bacteria are able to adapt to these foreign chemicals, gaining increased levels of tolerance and increased rates of xenobiotic degradation. On the strain level, increased tolerance can be caused by mutations in individual cells or through the acquisition of genes from other cells. At the …


Fast-Forward Protein Folding And Design: Development, Analysis, And Applications Of The Fast Sampling Algorithm, Maxwell Isaac Zimmerman Aug 2019

Fast-Forward Protein Folding And Design: Development, Analysis, And Applications Of The Fast Sampling Algorithm, Maxwell Isaac Zimmerman

Arts & Sciences Electronic Theses and Dissertations

Molecular dynamics simulations are a powerful tool to explore conformational landscapes, though limitations in computational hardware commonly thwart observation of biologically relevant events. Since highly specialized or massively parallelized distributed supercomputers are not available to most scientists, there is a strong need for methods that can access long timescale phenomena using commodity hardware. In this thesis, I present the goal-oriented sampling method, Fluctuation Amplification of Specific Traits (FAST), that takes advantage of Markov state models (MSMs) to adaptively explore conformational space using equilibrium-based simulations. This method follows gradients in conformational space to quickly explore relevant conformational transitions with orders of …


Characterizing And Modeling Antibiotic Resistance Dynamics In Diverse Microbial Communities, Molly Krisann Gibson Aug 2015

Characterizing And Modeling Antibiotic Resistance Dynamics In Diverse Microbial Communities, Molly Krisann Gibson

Arts & Sciences Electronic Theses and Dissertations

Complex microbial communities colonize every habitat investigated to date, including soil, animals, water, and humans, as well as the structures we live in. It has been hypothesized that there is network of exchange allowing both bacterial organisms and functions to seamlessly move between and within these environments. These microbial communities often serve essential and beneficial functions for the host organism or environment. This is particularly evident in the human gut, where microbial communities consistently provide a set of services to its human host, including protecting against enteric pathogens, liberating nutrients from food, and signaling immune system regulation. However, these communities …