Life Sciences Commons^™

The Role Of L-Alanine Signaling In Aspergillus Fumigatus Biofilm Adherence, Carbon Catabolism, And Echinocandin Susceptibility., Joshua D. Kerkaert

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is a saprophytic filamentous fungus that participates in environmental carbon and nitrogen cycles through the degradation of complex organic substrates. In addition to its ecological role, A. fumigatus is the primary causative agent of a spectrum of diseases depending on the immune status of the individual, the most lethal of which is invasive aspergillosis (IA). Treatment strategies for IA are limited and far too frequently fail. Despite the high rates of treatment failure, antifungal resistance remains relatively low, albeit rising at a concerning rate. Insights into this discrepancy between the rate of treatment failure and the rate of …

Links Between Electrophilic Stress And Antifungal Resistance In Pathogenic Candida Species, Amy R. Biermann

Dartmouth College Ph.D Dissertations

Collectively, Candida species are the most prevalent cause of both superficial and invasive fungal infections worldwide. Invasive Candida infections have a high mortality rate and predominantly affect individuals with underlying diseases, such as diabetes, HIV, or cancer. Unfortunately, many invasive Candida infections are recalcitrant to antifungal treatment, while intrinsically multidrug-resistant pathogens, like Candida auris, are increasing in prevalence. Although the canonical mechanisms of antifungal resistance in Candida species are well established, i.e., overexpression of efflux pumps and overexpression of or mutations in genes encoding drug targets, factors affecting the natural evolution and regulation of resistance mechanisms remain poorly understood. …

Regulation Of Skeletal Muscle Plasticity By The Gut Microbiome, Taylor R. Valentino

Theses and Dissertations--Physiology

Recent evidence suggests that the gut microbiome could play a role in skeletal muscle plasticity, providing novel treatments for muscle wasting diseases and/or performance enhancements. I first sought to determine if the gut microbiome is necessary for skeletal muscle adaptation to exercise. Forty-two, four-month old, female C57Bl/6J underwent nine weeks of weighted wheel running or remained in cage with a locked wheel, without or without the administration of antibiotics (treated). In response to wheel running, I found that antibiotic depletion of the microbiome led to a blunted hypertrophic response in the soleus muscle as measured by normalized muscle wet weight …

Metabolic Heterogeneity And The Roles Of Cody And Ccpa In Central Metabolism And S. Aureus Biofilm Formation., Logan L. Bulock

Theses & Dissertations

Staphylococcus aureus is a metabolically versatile human pathogen, causing disease in many areas of the body. Its versatility can be attributed to the fact that it utilizes a variety of tools to adapt to many different environments, including toxins to scavenge from the host and multiple transporters to compete for its preferred carbon sources. S. aureus can also survive in harsh conditions through biofilm development, which are notoriously recalcitrant to antibiotics and immune defenses. Biofilms exhibit marked heterogeneity, with division of labor for production of matrix components and differential gene expression among various niches within the biofilm.

In this study, …

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse

Arts & Sciences Electronic Theses and Dissertations

Malaria is an enormous financial and public health burden for much of the world, infecting over 200 million and killing over 400,000 people every year. While much progress has been made combating malaria in the past few decades, those advances have slowed in recent years, partially due to the emergence of resistance to all known antimalarials used to date. To achieve the goal of eliminating malaria as a major global health problem, new therapeutics need to be developed, targeting novel categories of parasite biology. One poorly understood area of parasite biology is the regulation of various metabolic pathways. We have …

Construction And Analysis Of Three Multi-Partite Synthetic Microbial Communities, Alexander J. Lazzara, Jacob K. Fanning

Honors Theses

Microbial Communities are of interest to molecular biologists hoping to understand the nature of metabolic interactions between co-existing, or possibly mutualistic, organisms. These interactions are ubiquitous in nature, but understanding the molecular mechanisms involved remains challenging and not well understood. Here, we design three tri-partite microbial circuits based on possible interactions among involved microbes, which are discussed and may suggest mutualistic interactions. Carbon and nitrogen molecular pathways and the intracellular metabolism of each microbe is discussed. We present minimal growth media that will ensure that organisms utilize available resources, which may originate from metabolic processes in neighboring microbes, simulating a …

How Acetylation Regulates Metabolic Enzyme Function During Environmental Shifts, Jared Canonigo

Biological Sciences Undergraduate Honors Theses

Organisms such as Saccharomyces cerevisiae can regulate the mechanisms of proteins through post-translational modification. These modifications play a vital role in functional proteomic activity because they can regulate protein activity, localization, and interaction with other cellular molecules. Such modifications include phosphorylation, methylation, and acetylation. The metabolic mechanisms of yeast became of keen interest to our lab because our lab noticed many stress defense proteins were being acetylated during stress heat shock. Notably, Adh1p and Adh2p showed both an increase and a decrease in acetylation at two lysine residues (K315 and K314) overtime during heat shock respectively, though the exact function …

Interregulation Between Msaabcr Operon And Ccpe To Determine Staphylococcal Metabolism And Virulence, Erin R. Cox

Honors Theses

Staphylococcus aureus is a complex human pathogen that causes problems in both healthcare and community settings. Staphylococcus aureus is a gram-positive, sphere shaped bacterium that usually colonizes in the nasal cavity of healthy individuals. Staphylococcus aureus infections are a growing health concern due to its ability to produce virulence factors, such as pigmentation, protease production, and capsule formation. Two regulators in S. aureus virulence factors are msaABCR, which is a newly characterized operon, and ccpE. In order to determine the interaction between these two regulators in regulating virulence and metabolism in S. aureus, ccpE and ccpE/ …

Study Of The Role Of The Msaabcr Operon In Tricarboxylic Acid Cycle Activity And Persister Cell Formation In Staphylococcus Aureus, Karsen Motter

Honors Theses

Staphylococcus aureus is an important human pathogen that causes wide arrays of infections ranging from minor skin infections to lethal systemic conditions such as infective endocarditis, osteomyelitis, sepsis and pneumonia. These systemic diseases are often difficult to treat due to the presence of persister cells. Persister cells are a phenotypic variant of the bacterial population that exhibit extreme and transient antibiotic tolerance accompanied by a transient halt in growth. Upon cessation of antibiotic treatment, however, persisters resume growth which results in recurrence of infections. This characteristic of persister cells therefore displays high clinical significance. In this study, we show the …

Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace

Theses and Dissertations (ETD)

Over the last century, the use of antibiotics has enabled many advances in modern medicine, making life as we know it possible. In recent years, however, emerging bacterial resistance to virtually all major antibiotic classes has resulted in a worldwide increase in morbidity, mortality, and financial burden associated with drug resistant infections. The antimicrobial resistance crisis presents an urgent need for new antimicrobials with distinct mechanisms of action from existing drugs. The current pharmaceutical pipeline of new antibiotics is limited due to three obstacles: a lack of understanding of resistance mechanisms, a dearth of novel mechanisms of action among new …

Investigating The Proteinaceous Regulome Of The Acinetobacter Baumannii, Leila G. Casella

USF Tampa Graduate Theses and Dissertations

Acinetobacter baumannii is an opportunistic pathogen that overtime has evolved into one of the most problematic pathogens due to its ability to overcome antibiotic pressures and harshly environments in the host and hospital environments. In this context, its genomic evolution due to its capacity to acquire genes that contribute to its pathogenic and antibiotic resistance nature has been the subject of research in the last decades providing with the identification of several proteins aiding in the process of pathogenicity. Although these findings have contributed to our understanding of A. baumannii pathogenic traits, the regulatory network that control their expression are …

Cyclic Adenosine Monophosphate Signaling In Mycobacterium Tuberculosis : New Insights Into A Universal Second Messenger, Richard Mcpherson Johnson

Legacy Theses & Dissertations (2009 - 2024)

Despite being the focus of intense research for many years Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the deadliest bacterial pathogen plaguing mankind today. Humans are the sole host and reservoir for Mtb, and Mtb has coevolved closely with its human host for thousands of years. Mtb currently infects over two billion people worldwide and over 1.5 million people die from TB each year, arguably making Mtb the most successful bacterial pathogen on the planet.

Mutual Regulation Of Crp And N(Epsilon)-Lysine Acetylation In Escherichia Coli, Robert James Davis

Dissertations

Post-translational modifications, such as N(epsilon)-lysine acetylation, are known to alter the behavior of transcriptional regulators in eukaryotes, but very little is known about the consequences of acetylation on transcriptional regulation in bacteria. Here, I provide evidence that a global transcriptional regulator of carbon metabolism, cAMP Receptor Protein (CRP), promotes both enzymatic and non-enzymatic lysine acetylation in E. coli. Non-enzymatic lysine acetylation occurs when cells ferment acetate, such as during growth on high concentrations of glucose. Intriguingly, CRP can be non-enzymatically acetylated on several lysines, including lysine 100 (K100). I provide evidence that neutralization of the K100 positive charge, as would …

Discovery And Characterization Of Bile Acid And Steroid Metabolism Pathways In Gut-Associated Microbes, Spencer Harris

Theses and Dissertations

The human gut microbiome is a complex microbial ecosystem residing in the lumen of our gastrointestinal tract. The type and amounts of microbes present in this ecosystem varies based on numerous factors, including host genetics, diet, and environmental factors. The human gut microbiome plays an important role in normal host physiological functions, including providing energy to colonocytes in the form of short-chain fatty acids. However, gut microbial metabolites have also been associated with numerous disease states. Current tools for analyzing the gut microbiome, such as high-throughput sequencing techniques, are limited in their predictive ability. Additionally, “-omic” approaches of studying the …

Amino Acid Catabolism In Staphylococcus Aureus, Cortney Halsey

Theses & Dissertations

Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in glutamate dehydrogenase (gudB), which generates 2-oxoglutarate from glutamate, abrogated growth in CDM suggesting …

Regulation Of Cid-Mediated Cell Death In Staphylococcus Aureus, Ian H. Windham

Theses & Dissertations

The death and lysis of a subpopulation of cells in Staphylococcus aureus biofilms is thought to benefit the surviving population by releasing extracellular DNA, a critical component of the biofilm extracellular matrix. Although the means by which S. aureus controls cell death and lysis is not completely understood, studies implicate the role of the cidABC, alsSD and lrgAB operons in this process. This dissertation has focused on the regulation of cidABC and alsSD expression, which is mediated, primarily, by the LysR-Type Transcriptional Regulator (LTTR) known as CidR. To better define the role of CidR in regulating cidABC and alsSD transcription …

Characterization Of The Ato Gene Family In Alternative Carbon Metabolism, Heather A. Danhof

Dissertations & Theses (Open Access)

As a commensal colonizer and opportunistic pathogen, Candida albicans is the most clinically important human associated fungus. Systemic infection carries an unacceptably high mortality rate of ~40% in the growing population of immunocompromised individuals. Macrophages are important innate immune cells that limit the niches in the human body in which C. albicans can persist through phagocytic removal. However, following phagocytosis C. albicans readily escapes from the immune cell by differentiating into filamentous hyphae, a process that should be inhibited in the normally acidic phagolysosome. We have shown that C. albicans induces germination by neutralizing the phagolysosome. To better understand this …

Lipoate Metabolism In Staphylococcus Aureus Pathogenesis, Maria Azul Zorzoli

Master's Theses

Lipoate is an essential cofactor of several proteins involved in cellular energy homeostasis and catabolism. Lipoate metabolism has been linked to pathogenesis in some microbial species, but its role in Staphylococcus aureus infections had not been explored. In this thesis, we tested the hypothesis that lipoate acquisition mechanisms promote S. aureus infectivity. We used a bacterial genetics approach to elucidate the biological function of the S. aureus genes involved in lipoate metabolism. Our findings allowed us to propose a model for lipoic acid de novo biosynthesis and salvage pathways in S. aureus. Moreover, we detail hitherto undescribed genetic arrangements of …

Identifying And Characterizing Yeast Pas Kinase 1 Substrates Reveals Regulation Of Mitochondrial And Cell Growth Pathways, Desiree Demille

Theses and Dissertations

Glucose allocation is an important cellular process that is misregulated in the interrelated diseases obesity, diabetes and cancer. Cells have evolved critical mechanisms for regulating glucose allocation, one of which is sensory protein kinases. PAS kinase is a key sensory protein kinase that regulates glucose allocation in yeast, mice and man; and is a novel therapeutic target for the treatment of metabolic diseases such as obesity, diabetes and cancer. Despite its importance, the molecular mechanisms of PAS kinase function are largely unknown. Through large-scale protein-interaction studies, we have identified 93 novel binding partners for PAS kinase which help to expand …

Elucidating The Impact Of Roseophage On Roseobacter Metabolism And Marine Nutrient Cycles, Nana Yaw Darko Ankrah

Doctoral Dissertations

As the most abundant biological entities in marine environments, viruses are an important component of marine food webs. The activity of viruses contributes significantly to the mortality of marine microorganisms, ultimately influencing biological function and chemical composition of aquatic systems by impacting species composition and flow of carbon, nitrogen and other nutrients. Despite the growing recognition that viral activity contributes to marine biogeochemical cycles, the extent to which virus infection reshapes host metabolism and the effect of this alteration on the composition of host lysate remains poorly understood. Additionally, the degree to which natural bacterioplankton communities metabolise the released lysate …

Role Of Crebh In Endotoxin Mediated Modulation Of Hepatic Metabolism, Aditya Prakash Dandekar

Wayne State University Dissertations

Bacterial endotoxins can induce a variety of physiological changes in the host. This effect is not only restricted to inflammatory changes but also comprises metabolic changes in the host body. Lipopolysaccharide (LPS), one of the key components of the bacterial cell walls, is capable of triggering host metabolic changes. Hyperlipidemia usually accompanies with high endotoxin levels as well as inflammation. Lipid metabolism disorders are one of the common hallmarks of a patient with sepsis or high levels of endotoxin through diet. Previously, we have identified an endoplasmic reticulum (ER) anchored liver-specific transcription factor CREBH (cAMP-responsive element-binding protein, hepatocyte-specific), which is …

Carnitine And O-Acylcarnitines In Pseudomonas Aerguinosa: Metabolism, Transport, And Regulation, Jamie Meadows

Graduate College Dissertations and Theses

Pseudomonas aeruginosa is found in numerous environments and is an opportunistic pathogen affecting those who are immunocompromised. Its large genome encodes tremendous metabolic and regulatory diversity that enables P. aeruginosa to adapt to various environments. We are interested in how P. aeruginosa senses and responds to the host-derived compounds, carnitine and acylcarnitines. Acylcarnitines can be hydrolyzed to carnitine, where the liberated carnitine and its catabolic product glycine betaine can be used as osmoprotectants, for induction of the virulence factor phospholipase C, and as sole carbon, nitrogen, and energy sources. P. aeruginosa is incapable of de novo synthesis of carnitine and …

Exploring The Role Of Intracellular Aminopeptidases In Staphylococcus Aureus Pathogenesis, Devon Nicole Marking

USF Tampa Graduate Theses and Dissertations

Staphylococcus aureus is a remarkably pathogenic bacterium that is widely prevalent among the human population. It is the leading agent of skin and soft tissue infections, and is also responsible for causing an array of severe and life threatening diseases. The invasiveness of the pathogen, coupled with increasing antibiotic resistance seen for S. aureus infections, makes this bacterium a prominent public health concern. The extended pathogenicity of S. aureus is largely due to its repertoire of virulence factors, which are typically characterized by being bound to the cell wall, or secreted into the extracellular environment. Previously, our lab identified a …

Cellular Metabolism And Its Effect On The Type Iii Secretion System Of Dickeya Dadantii 3937, William Cortrell Hutchins

Theses and Dissertations

Nutrition, in both eukaryotes and prokaryotes, is vital to the life and well-being of the species. In organisms such as Escherichia coli, metabolism and its regulation have been well established, whereas in Dickeya dadantii 3937, the metabolic pathways and their effects on other processes have not been elucidated. Little is known is how carbon metabolism is able to regulate virulence and pathogenicity in this organism. In this work, we have investigated how the metabolic network contributes to positively and negatively regulating the pathogenicity of Dickeya dadantii 3937.

Chapter 1 provides an overview of the history and virulence processes in …

Determining The Influence Of The Extracellular Proteinase From Brevibacterium Linens On The Metabolism Of Lactococcus Lactis Spp. Lactis Using Functional Genomics, Yi Xie

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Since the catabolism of amino acids in cheese results in the formation of most volatile flavor compounds, a proper intracellular pool of amino acids must be established in order to produce a desirable flavor production in cheese. Generation of this pool of amino acids requires complex interactions among casein and its derivatives, proteolytic enzymes, and transport systems in the associated bacteria, including lactococci. In this project, we hypothesized that casein hydrolysis by the extracellular proteinases of Brevibacterium linens BL2 modulates the expression profile of proteolytic related genes in Lactococcus lactis spp. lactis IL1403.

In order to monitor the …

The Role Of D-Gluconic Acid In The Regulation Of The Synthesis Of The Enzymes Of The Entner-Doudoroff Pathway In Pseudomonas Fluorescens, Steven C. Quay

Honors Theses

Induction of Entner-Duodoroff pathway enzymes in Pseudomonas fluorescens was investigated to study the role of gluconate as a possible inducer. Glucose oxidase-deficient mutants were isolated and characterized. One of these mutants, gox-7, was deficient in particulate glucose oxidase; another mutant, gox-17, was deficient in particulate glucose and gluconate oxidase activities. Gluconate, but not glucose, induced synthesis of gluconokinase and 6-phosphogluconate dehydratase in both mutants. High constitute levels of 2-keto-3-deoxy-6-phosphogluconate aldolase were found when both mutants were grown on glucose. Growth of parent and both mutant strains on glycerol also resulted in high levels of Entner-Doudoroff pathway enzymes. It was concluded …