Life Sciences Commons^™

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

Editorial: New Frontiers In The Application Of Stable Isotopes To Ecological And Ecophysiological Research, Keith A. Hobson, John P. Whiteman, Seth D. Newsome

Biological Sciences Faculty Publications

No abstract provided.

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 …

The Role Of Cd5 In Cd4+ T Cell Metabolism, Joshua Bennett, Kiara Whitley, Claudia Freitas Phd, Christopher Haynie, Carlos Moreno, Scott Weber

Library/Life Sciences Undergraduate Poster Competition 2022

T cells serve a key role in the immunological response in the adaptive system. Different receptors present on the T cell have certain roles and are able to either inhibit or stimulate signaling which consequently regulates the function and metabolism of the cell. CD5 is an inhibitory co receptor expressed on the surface of T cells known to regulate thymocyte selection and TCR signaling . Our goal is to better understand the effects of CD5 regulation in metabolism. Using metabolic flux assays, we found that CD5KO naïve T cells have increased glycolysis and mitochondrial respiration in comparison to wild type …

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 …

Glycolic Acid Utilization In Two Species Of Marine Bacteria, Erik S. Timsak

STAR Program Research Presentations

Interactions between bacteria and phytoplankton are crucial for the cycling of organic matter in marine environments. Around 50% of organic carbon taken up by marine bacteria is converted into inorganic carbon. The uptake of organic carbon by marine bacteria exuded from phytoplankton is a key factor in regulating the marine carbon cycle. One such molecule that is exuded by phytoplankton and then uptaken by marine bacteria is called glycolate - the anion of glycolic acid, a two caron molecule. Glycolate is exuded by phytoplankton during photorespiration and 10-50% of dissolved organic carbon in marine environments is comprised of glycolate. Additionally, …

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 …

The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Dwight Forshee

ELAIA

The microbiome is a dynamic community that can positively and negatively influence host health. Lactobacillus reuteri is a probiotic that has received much attention for its ability to inhibit pathogens such as Salmonella typhimurium, Escherichia coli, and Clostridium difficile. It does so by its unique ability to metabolize glycerol into the antimicrobial compound 3-HPA, which is commonly referred to as reuterin. The ability to secrete reuterin is dependent not only on glycerol availability but also the concentration of glucose. In fact, there appears to be a “goldilocks” ratio between glucose and glycerol as either too much or too little …

A Broad Spectrum Racemase In Pseudomonas Putida Kt2440 Plays A Key Role In Amino Acid Catabolism, Atanas D. Radkov, Luke A. Moe

Plant and Soil Sciences Faculty Publications

The broad-spectrum amino acid racemase (Alr) of Pseudomonas putida KT2440 preferentially interconverts the L- and D-stereoisomers of Lys and Arg. Despite conservation of broad-spectrum racemases among bacteria, little is known regarding their physiological role. Here we explore potential functional roles for Alr in P. putida KT2440. We demonstrate through cellular fractionation that Alr enzymatic activity is found in the periplasm, consistent with its putative periplasm targeting sequence. Specific activity of Alr is highest during exponential growth, and this activity corresponds with an increased accumulation of D-Lys in the growth medium. An alr gene knockout strain (Δalr) was generated …

The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Forshee

Honors Program Projects

The microbiome is a dynamic community that can positively and negatively influence host health. Lactobacillus reuteri is a probiotic that has received much attention for its ability to inhibit pathogens such as Salmonella Typhimurium, Escherichia coli, and Clostridium difficile. It does so by its unique ability to metabolize glycerol into the antimicrobial compound 3-HPA, which is commonly referred to as reuterin. The ability to secrete reuterin is dependent not only on glycerol availability but also the concentration of glucose. In fact, there appears to be a “goldilocks” ratio between glucose and glycerol as either too much or too …

The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Forshee

Scholar Week 2016 - present

The microbiome is a dynamic community that can positively and negatively influence host health. Lactobacillus reuteri is a probiotic that has received much attention for its ability to inhibit pathogens such as Salmonella Typhimurium, Escherichia coli, and Clostridium difficile. It does so by its unique ability to metabolize glycerol into the antimicrobial compound 3-HPA, which is commonly referred to as reuterin. The ability to secrete reuterin is dependent not only on glycerol availability but also the concentration of glucose. In fact, there appears to be a “goldilocks” ratio between glucose and glycerol as either too much or too …

Is There A Link Between Aging And Microbiome Diversity In Exceptional Mammalian Longevity?, Graham M. Hughes, John Leech, Sebastien J. Puechmaille, Jose V. Lopez, Emma C. Teeling

Biology Faculty Articles

A changing microbiome has been linked to biological aging in mice and humans, suggesting a possible role of gut flora in pathogenic aging phenotypes. Many bat species have exceptional longevity given their body size and some can live up to ten times longer than expected with little signs of aging. This study explores the anal microbiome of the exceptionally long-lived Myotis myotis bat, investigating bacterial composition in both adult and juvenile bats to determine if the microbiome changes with age in a wild, long-lived non-model organism, using non-lethal sampling. The anal microbiome was sequenced using metabarcoding in more than 50 …

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.

Evolutionary Enhancement Of Zika Virus Infectivity In Aedes Aegypti Mosquitoes, Yang Liu, Jianying Liu, Senyan Du, Cheng-Feng Qin, Penghua Wang, Pei-Yong Shi, Gong Cheng

NYMC Faculty Publications

Zika virus (ZIKV) remained obscure until the recent explosive outbreaks in French Polynesia (2013-2014) and South America (2015-2016). Phylogenetic studies have shown that ZIKV has evolved into African and Asian lineages. The Asian lineage of ZIKV was responsible for the recent epidemics in the Americas. However, the underlying mechanisms through which ZIKV rapidly and explosively spread from Asia to the Americas are unclear. Non-structural protein 1 (NS1) facilitates flavivirus acquisition by mosquitoes from an infected mammalian host and subsequently enhances viral prevalence in mosquitoes. Here we show that NS1 antigenaemia determines ZIKV infectivity in its mosquito vector Aedes aegypti, which …

Draft Nuclear Genome Sequence Of The Liquid Hydrocarbon–Accumulating Green Microalga Botryococcus Braunii Race B (Showa), Daniel R. Browne, Jerry Jenkins, Jeremy Schmutz, Shengqiang Shu, Kerrie Barry, Jane Grimwood, Jennifer Chiniquy, Aditi Sharma, Thomas Daniel Niehaus, Taylor L. Weiss, Andrew T. Koppisch, David T. Fox, Suraj Dhungana, Shigeru Okada, Joe Chappell, Timothy P. Devarenne

Plant and Soil Sciences Faculty Publications

Botryococcus braunii has long been known as a prodigious producer of liquid hydrocarbon oils that can be converted into combustion engine fuels. This draft genome for the B race of B. braunii will allow researchers to unravel important hydrocarbon biosynthetic pathways and identify possible regulatory networks controlling this unusual metabolism.

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 …

Identification And Analysis Of Bacterial Genomic Metabolic Signatures, Nathaniel Bowerman, Nathan L. Tintle, Matthew Dejongh, Aaron A. Best

Faculty Work Comprehensive List

With continued rapid growth in the number and quality of fully sequenced and accurately annotated bacterial genomes, we have unprecedented opportunities to understand metabolic diversity. We selected 101 diverse and representative completely sequenced bacteria and implemented a manual curation effort to identify 846 unique metabolic variants present in these bacteria. The presence or absence of these variants act as a metabolic signature for each of the bacteria, which can then be used to understand similarities and differences between and across bacterial groups. We propose a novel and robust method of summarizing metabolic diversity using metabolic signatures and use this method …

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 …

Elucidating The Role Of Mifs-Mifr Two-Component System In Regulating Pseudomonas Aeruginosa Pathogenicity, Gorakh Digambar Tatke

FIU Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative, metabolically versatile, opportunistic pathogen that exhibits a multitude of virulence factors, and is extraordinarily resistant to a gamut of clinically significant antibiotics. This ability is in part mediated by two-component systems (TCS) that play a crucial role in regulating virulence mechanisms, metabolism and antibiotic resistance. Our sequence analysis of the P. aeruginosa PAO1 genome revealed the presence of two open reading frames, mifS and mifR, which encodes putative TCS proteins, a histidine sensor kinase MifS and a response regulator MifR, respectively. This two-gene operon was found immediately upstream of the poxAB operon, where poxB encodes …

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 …

The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader

Senior Honors Theses

Metabolic disorders affect around thirty-four percent of the population in the United States. Among these disorders is lactose intolerance, which results from diminished production of the human lactase enzyme. This disorder and others like it are genetically determined and cannot be cured. However, the use of transformed bacteria implanted in the colon may provide a means by which the faulty pathway can be bypassed. To test whether transformed bacteria have the capability to aid in the digestion of normally indigestible compounds, a transformed strain of Escherichia coli overexpressing the beta-galactosidase enzyme encoded by the lacZ gene was colonized in the …