Digital Commons Network^™

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Commentary On Blaser's "Antibiotic Use And Its Consequences For The Normal Microbiome", Fred C. Tenover

AMR Commentary

If you have not read this eye-opening commentary by Dr. Martin Blaser about the negative impact of the widespread use of antibiotics in children, you should. The goal of giving antibiotics to children usually is to treat an infection — an earache, a respiratory tract infection, or perhaps a potentially deadly bloodstream infection. Those antibiotics, however, will often kill more than just the bacteria that are causing the infection. Humans have large quantities of “good bacteria” in our intestinal tracts, on our skin, and elsewhere on our body that play an important role in keeping us healthy.

Skin Bacteriome Structure And Batrachochytrium Dendrobatidis Prevalence Differs Amongst Two Sympatric Salamanders In The San Francisco Bay Area., Aria Norwood, Jadyn Jamora, Micuel Madison, Jamiee Nguyen, Azan Yousaf, Katya Morales, Emily Vu, Obed Hernández-Gómez

Natural Sciences and Mathematics | Student Professional Publications

Microbial surveys are becoming an important component of wildlife health research, especially in cases where environmental change and infectious diseases are serious issues. Amongst amphibians, Batrachochytrium spp. have the potential to be fatal pathogens that can impact the population health of numerous species. We assessed the skin bacteriome, prevalence of Batrachochytrium dendrobatidis (Bd) and body conditions of two salamander genera with different life histories: the California slender salamander (Batrachoseps attenuatus) and members of the Pacific newt species complex (Taricha torosa and Taricha granulosa; Taricha sp.). We used 16S rRNA V4 amplicon sequencing to characterise the bacterial communities. Taricha sp. had …

The Impact Of Polymycovirus 1 On Aspergillus Fumigatus Pathogenesis During Lung Infection, Alexander W. Rapp

Dartmouth College Ph.D Dissertations

The genus Aspergillus comprises over 250 species of fungi. Within this genus, only a handful of species cause disease in humans. One species is Aspergillus fumigatus (A.f.), an environmentally ubiquitous, saprophytic fungal pathogen. Lung infections due to A.f. range from invasive infection to allergic forms of the disease. Allergic bronchopulmonary aspergillosis (ABPA) is one of the most severe forms and presents as a hypersensitivity that often results in off-target damage to the surrounding airways. Patients with ABPA are sensitized to fungal antigens and this is commonly seen in cystic fibrosis and genetic predispositions. Recent data from our lab shown how …

Functional Characterization Of Uncharacterized Essential Genes In The Oral Pathogen Streptococcus Mutans, Courtney Dover

Student Theses and Dissertations

Streptococcus mutans is a pathogen associated with the formation of dental caries, and its genome contains many uncharacterized genes, including some which are classified as essential genes. These genes are required for the growth of the organism. Characterizing the function of these genes is important for understanding the organism, as well as identifying potential antimicrobial targets. This project used a CRISPRi (CRISPR interference) system to repress seven experimentally uncharacterized genes within the S. mutans genome and investigated the effects of their repression via RNA-seq transcriptomics, phylogenetic analysis, and TEM. The gene annotated as SMU_393 was then prioritized for further analysis …

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

Seroprevalence And Associated Risk Factors Of Caprine Arthritis Encephalitis (Cae) And Peste Des Petits Ruminants (Ppr) Among Deer In An Institutional Farm In Malaysia, Krishnan Nair Balakrishnan, Faez Firdaus Abdullah Jesse, Bura Thlama Paul, Shalonagiftsal Stephen C Charles, Ummul Rifhan Najiha Noor Zaman, Eric Lim Teik Chung, Nur Amira Azhar, Abdirahman Barre, Muhammed Mikail, Mohd Azmi Mohd Lila

The Thai Journal of Veterinary Medicine

Caprine arthritis encephalitis (CAE) and peste des petits ruminants (PPR) are significant viral diseases impacting small ruminants, leading to substantial economic losses and posing a potential threat to livestock health. Although seroprevalence evidence of these viruses has been documented in ruminants, there is a lack of data regarding their presence among farmed deer in Malaysia. This preliminary study aimed to determine the seroprevalence and associated risk factors for CAEV and PPRV infections among deer in Malaysia. A total of ninety-two blood sera from an institutional deer farm were screened for CAEV and PPRV antibodies using commercially available indirect ELISA test …

From Epidemics To Experimental Treatments: Amphibian Mass Mortality Events And A Potential Treatment For Chytridiomycosis, Daniel Callahan

Graduate Masters Theses

Worldwide, amphibian populations have experienced dramatic declines due to a variety of threats. Among them, disease has been particularly deleterious and continues to impact populations. In the United States and Canada, the three leading causes of amphibian mass mortality events are ranavirosis, chytridiomycosis, and severe perkinsea infection, all caused by infectious pathogens. While research and policy have helped populations recover from these diseases, more work needs to be done to develop practical and efficient treatments for these infections. Of these three diseases, chytridiomycosis has had the most devastating effects on amphibian populations globally. Caused by the chytrid fungi Batrachochytrium dendrobatidis …

Characterization Of Sars-Cov-2 Replication And Transcription Complexes Via Structural And Evolutionary Approaches, Amelie Ghirardo, Ben Shabatian, Avishai Aghelian, Kyle Tau, Eleonora Gianti

Undergraduate Research

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused around 700M cases and over 7M COVID-19-related deaths recorded worldwide (World Health Organization, March 2025). Aiming to effectively combat this and other disease-causing Coronaviruses (CoV), unprecedented research efforts led to the development of new vaccines and antiviral therapies. Due to emergence of variants of concern (VOCs) with increased transmissibility, immune evasion from vaccination, and potential to resist the available treatments, SARS-CoV-2 continues to represent a major threat to global health. Hence, there is a pressing need to discover new antivirals with broad-spectrum efficacy against multiple SARS-CoV-2 variants and related CoVs. This project …

Viral Detection In Anterior Nasal Swabs Versus Nasopharyngeal Swabs In Children, Nicole Neeley, Abby Kietzman, Rangaraj Selvarangan, Dithi Banerjee, Jennifer Goldman, Jennifer Schuster

Research Days

Background: Respiratory viruses are a significant cause of pediatric illness and healthcare utilization. Diagnostic testing for respiratory viruses is generally performed using nasopharyngeal (NP) specimens obtained by trained staff, limiting testing to medical settings. Evaluating additional sampling methods in children that are easier to collect and can be performed outside of medical settings, such as anterior nasal swab (NS) specimens may expand access to diagnostic testing and aid public health surveillance.

Methods: Eligible children hospitalized at Children’s Mercy Hospital who had a standard of care NP specimen collected for respiratory viral testing were enrolled. Research NS specimens were obtained through …

In The Quest For New Horizons: Evaluating Novel Therapeutic Approaches For Tuberculosis Treatment, Selassie Mawuko, Aminata Traore, Bibi-Sakeena Khemraj, Anna Steto, Richa Gupta

Publications and Research

Tuberculosis (TB) in humans, caused by Mycobacterium tuberculosis, is a significant global health concern, resulting in high disease burden and mortality each year which together make it the world’s topmost infectious killer. The emergence of multidrug-resistant tuberculosis (MDR-TB) in recent decades has further exacerbated the present situation and warrants an urgent need to develop and investigate innovative treatment regimes. This study aims to assess the therapeutic potential of newly identified drug candidates, namely Bedaquiline, Delamanid, and Linezolid, in treating MDR-TB. We adopted a consolidated and integrated approach encompassing a thorough literature review, empirical experimental studies, multiple sequence alignments, and …

Relationship Between Prodigiosin Production And Batrachochytrium Dendrobatidis Metabolite Concentration, Nautica Ek Hagg

Honors Thesis

Batrachochytrium dendrobatidis (Bd) is a pathogenic fungus that has been causing extirpations of amphibian species across the globe. The microbiome on the skin of amphibians is known to be a key factor in infection dynamics. It has been established that one species of cutaneous bacteria, Serratia marcescens, and a secondary metabolite with antifungal properties it produces, prodigiosin, has shown a promising ability to decrease the growth of Bd. However, when Serratia marcescens is grown in the same media with added metabolites produced by Bd, there is an observed decrease in the production of the bacteria’s protective metabolite, prodigiosin. This experiment …

Intrinsic And Extrinsic Drivers Of Bioaerosol Decay: Investigating Pathogen Stability Of Bacteriophage Ms2, Sin Nombre Virus, And Sars-Cov-2 In Simulated Environments, Elizabeth A. Klug

Theses & Dissertations

The threat posed by a virus as a bioaerosol depends largely on its stability under various environmental conditions (relative humidity (RH), sunlight, ozone, etc.). This stability is typically studied through aerosol decay—how the virus' viability changes over time when exposed environmental conditions. The Goldberg rotating drum, a widely used tool for studying bioaerosols, has been the basis of such research (Goldberg et al., 1958). However, it has significant limitations, including an inability to measure initial pathogen infectivity loss and the use of small sample volumes. Additionally, it does not answer the question of what intrinsic factors (lipids, proteins, nucleic acids) …

Pseudomonas Aeruginosa Exoy Enzymatic Activity Inhibits Exos-Induced Caspase-3/7 Activation But Not Cytotoxicity In Pmvecs, Connor Holm

Poster Presentations

Pseudomonas aeruginosa (P. aer.) is the most common cause of ventilator associated pneumonia (VAP) in ICU patients. Different combinations of exoenzymes (S, T, Y, and U) are found in P. aer. strains. ExoY is most often associated with VAP in ICU patients. ExoY infection of pulmonary microvascular endothelial cells (PMVECs) induces cell rounding but does not activate intracellular caspase-3/7 or cause cell death. ExoS and ExoT infection of epithelial cells leads to caspase-3/7 dependent cell death. Previous studies using epithelial cells show that ExoY alleviates the cytotoxic effects of ExoS and ExoT. Here, we sought to determine whether ExoY inhibits …

Novel Chloroviruses With Unique Glycans On Their Major Capsid Proteins, Cayden J. Homolka

Honors Program: Senior Projects (Public)

Chloroviruses, of the family Phycodnaviridae, are large, dsDNA viruses with a genome of 290 to 410 kb. These virus genomes are so large that they are classified as “giant viruses”. Within this genome, up to 16 tRNAs and 330 to 450 proteins are encoded. Among the massive amounts of genes and proteins are unique carbohydrate synthesis/metabolism genes, which are responsible for the glycosylation of chloroviruses major capsid proteins. In most viruses, these proteins are glycosylated by the host enzymes located in the endoplasmic reticulum. Instead, Chloroviruses encode their own glycosylation machinery; essentially decorating themselves. Furthermore, these chlorovirus glycans are unlike …

Pseudomonas Aeruginosa Exoenzyme Y Enzymatic Activity Inhibits Exoenzyme S-Induced Caspase Activation But Not Cytotoxicity In Pulmonary Microvascular Endothelial Cells, Connor Holm

Honors Theses

Pseudomonas aeruginosa (P. aeruginosa) is the most common cause of ventilator-associated pneumonia in intensive care unit patients. P. aeruginosa utilizes a type III secretion system that injects exoenzymes U, S, T, and/or Y into the host cell cytosol. A majority of clinically isolated P. aeruginosa strains express ExoY often in combination with ExoU and ExoT, or ExoS and ExoT. Host signaling mechanisms in response to intoxication with individual exoenzymes have been extensively studied, yet little is known about host cell response to co-intoxication. In this study, pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains expressing different combinations …

Sars-Cov-2 Modulates Pla2g2d/Pgd2 Signaling To Manipulate Host Immune Response To Increase Disease Severity., Dante L. Hamiel

Electronic Theses and Dissertations

Background: Previous studies suggested that SARS-CoV-2 infection could cause diverse immune and metabolic dysregulations, although the underlying mechanisms remain poorly understood. In addition, viruses may escape the immune response by modulating cellular metabolism, mitochondria, and protein functions indicating that immune or metabolic components may represent novel targets for anti-viral strategies. However, whether immune and metabolic disorders interact or affect each other waits to be determined. On the other hand, previous investigations identified the critical roles of a cell membrane-bound phospholipase PLA₂G2D and its downstream products PGD₂ in regulating the metabolism and inflammation in respiratory system. More importantly, …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

A Multi-Tiered Approach To Improving Vaccination: Adjuvanticity, Alternate Routes Of Delivery, And Science Communication, Haley Agnes Bridgewater

Boise State University Theses and Dissertations

Vaccines have been used to prevent infectious disease for over 200 years. While they are an incredible way to prevent loss of life, they can be improved upon. Researchers around the globe are working to improve the immune response and ultimately the protection provided by existing and new vaccines. In this dissertation, I investigate three ways to improve vaccine immune responses: using an adjuvant, using a prime-boost intramammary delivery route in cows, and using microneedle delivery route. Cholera toxin (CT) is a bacterial toxin that has a non-toxic B subunit (CTB) used as a vaccine adjuvant. However, little is known …

Phosphatase Activity And Structure Of The Spoiie Protein In Clostridioides Difficile, Kathryn Wootten

Biological Sciences Undergraduate Honors Theses

Clostridioides difficile is a major cause of severe gastrointestinal infections and diseases, particularly in healthcare settings. Because of its ability to produce infectious endospores by sporulation, the protein SpoIIE, which is known to play a role in the regulation of this process, is being explored as a potential therapeutic target. In order to gain better insight into the structure and function of this protein, a concentrated and purified sample of the protein must be obtained. The goal of this study was to determine the conditions that would yield the highest amount of SpoIIE. The density of the cultures of bacteria …

Serological Evaluation For Leptospirosis On Samples Received By The Connecticut Veterinary Medical Diagnostic Laboratory (Cvmdl), Hayden R. Samuels

Honors Scholar Theses

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic species of Leptospira, motile spirochetes capable of infecting humans and animals. Transmission typically occurs through contact with water or soil contaminated by the urine of reservoirs or infected animals. Although leptospirosis is considered a neglected tropical disease, its geographic range is expanding due to climate change and urbanization. Surveillance remains limited in many regions, especially in the United States. This study aimed to assess the seroprevalence and serovar diversity of Leptospira exposure in a variety of domestic and wild animals submitted to the Connecticut Veterinary Medical Diagnostic Laboratory (CVMDL). …

Impact Of Temperature And Microbial Infection On The Honey Bee Hemocytes, Michael E. Oeth

Master's Theses

Introduction

Honey bees (Apis mellifera) rely on hemocytes for immunity, wound healing, and hemolymph homeostasis. While 32°C reflects optimal hive conditions, suboptimal temperatures (22°C) and stressors like pathogens (Varroa destructor, bacteria) or pesticides impair hemocyte function. Using clodronate liposomes (CLD) to deplete hemocytes, we assessed how immune suppression interacts with these stressors.

Methods

Newly emerged (5-day-old) and older (15-day-old) bees were assigned to: CLD, control liposomes (LP), PBS, injection wound, or no treatment. Cohorts were exposed to 32°C (optimal) or 22°C (stressful for non-immunosuppressed bees). Fifteen-day-old bees were challenged with Escherichia coli or Staphylococcus aureus. Survival, hemolymph volume, and hemocyte …

Mechanisms Of Behavioral Change In Hosts Of Toxoplasma Gondii: A Review, Olivia Grimsley

Senior Honors Theses

The parasite Toxoplasma gondii is a highly ubiquitous parasite that latently infects an estimated 33% percent of the global population. Toxoplasmosis is of obvious clinical significance due to the extremely high risks to the unborn who contract it congenitally. Less attention has been given to a more subtle aspect of latent infection, which is the behavioral alterations that are commonly experienced by those who contract the parasite. Infected individuals commonly display a variety of altered behaviors, such as increased aggression and risk-seeking behaviors, depression, higher tendency towards suicide and self-directed violence, a loss of fear response, and a greatly increased …

The Roles Of Rnt1 And Putative Endoribonucleases In Eukaryotic Mrna Degradation, Lee-Ann Notice-Sarpaning

Dissertations and Theses (Open Access)

Endoribonucleases initiate degradation by cleaving RNAs internally. Mutations in these enzymes have been shown to cause diseases such as cancer, developmental disorders, and neurodegenerative diseases. Yet, eukaryotic endoribonucleases have not been well studied, especially with regard to their role in nuclear mRNA degradation. Rnt1 is a Saccharomyces cerevisiae (budding yeast) nuclear endoribonuclease and homolog of human Drosha with well-characterized roles in the processing of ncRNAs. The enzyme recognizes and cleaves double-stranded RNA stems containing a terminal tetraloop with an AGNN consensus sequence. However, the scope and consequence of its function in mRNA degradation has heretofore been unclear. Previous studies have …

Differential Progression Of Pancreatic Premalignancy In Geographically Distant Murine Transgenic Cohorts Uncovers Key Role Of Microbial Metabolites, Rian M. Howell

Dissertations and Theses (Open Access)

Cancer is a leading cause of death worldwide. Despite recent advances in diagnostic and therapeutic modalities, pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that remains highly lethal. Efforts have been made to increase the understanding of the underlying mechanisms driving early stages of tumor development, when the cancer is most susceptible to intervention. To this end, genetically engineered mouse models (GEMMs) have been developed with the mutations most commonly seen in the patient population. Expression of these mutations in select cellular compartments has resulted in the ability to recapitulate characteristics of human pancreatic cancer such as the development of …

Navigating The Challenges Of Coccidioides Surveillance: Insights From The Environment Of El Paso County, Texas, Tanzir Hossain

Open Access Theses & Dissertations

Coccidioidomycosis, or Valley fever, is a fungal infection resulting from the inhalation of spores from the Coccidioides species (C. immitis and C. posadasii), native to arid areas of the Western Hemisphere. Coccidioidomycosis presents considerable health hazards and can be fatal. It affects between 206,000 and 360,000 individuals annually, leading to 700 to 1,100 fatalities in the United States alone. In response to these issues, extensive research has concentrated on therapeutic goals for this infectious disease. Nonetheless, more limited research has focused on the environmental detection of its causative fungi, which is crucial for forecasting treatment needs and formulating preventive strategies. …

Characterization Of Streptococcus Gallolyticus: An Emerging Pathogen Causing Turkey Streptococcosis, Latasha S. Gray

Graduate Theses and Dissertations

During the past five years, there has been an increased occurrence of Streptococcus gallolyticus in young turkey poults. This emerging pathogen previously affected turkey flocks without any indication of disease prior to acute mortality. However, recently there has been two cases of neurological presentation associated with S. gallolyticus subsp. pasteurianus that are unique to traditional disease presentation in turkey poults. The objectives of the present dissertation were to compile data associated with the two neurological cases and compare different S. gallolyticus strains as well as pathogenic Enterococcus cecorum to the neurological strains. The two neurological cases occurred between July and …

Bacterial Chondronecrosis With Osteomyelitis In Broilers: Etiology And Selected Mitigation Measures, Khawla Saud Alharbi

Graduate Theses and Dissertations

Bacterial chondronecrosis with osteomyelitis (BCO) is the predominant cause of lameness in broiler chickens. It mainly impacts broiler production and animal welfare, causing substantial financial losses accounting for 1- 2% due to bird condemnations at the marketing age. Remediating BCO lameness disease demands investigating its causes using appropriate models and evaluating preventive measures, such as enhancing epithelial tissue health and tight junction integrity in the digestive and respiratory tract, strengthening immune functions, and improving bone strength. Therefore, the objectives of this dissertation were to 1) study predisposing factors for BCO lameness by investigating the effects of deoxynivalenol (DON) and fumonisin …

Bibliometric Analysis Of Research Trends Related To Human Immunodeficiency Virus., Madyson E. Johnson, Kaitlyn R. Coffman, Valerie Rivas, Elizabeth Barrett

ATU Scholars Symposium

Human immunodeficiency virus poses major health burden across the globe including the United States of America and has its zoonotic origin from the Simian Immunodeficiency viruses of sooty mangabey monkey and chimpanzee in Africa. Epidemiological trends indicate that even though the mortality rates for HIV are falling globally, the rates of new cases have been rising since 2010 in several countries including the USA. An estimated 0.5% of the human population is currently infected with the virus with countries like USA, India, Nigeria and South Africa carrying the highest burden of the disease. Host receptors such as CD4 and coreceptors …

From Dysbiosis To Dysfunction: Investigating The Effects Of Chronic Cocaine Use On Oral Microbial Shifts And Neuropathogenesis, Douglas E. Johnson

MUSC Theses and Dissertations

Cocaine use disorder remains a significant public health challenge. However, the mechanisms by which chronic cocaine use contributes to neuroinflammation and cognitive decline are still not fully understood. Chronic non-intravenous cocaine use is associated with oral microbial dysbiosis. Although the gut-brain axis has been widely studied, the impact of cocaine-mediated shifts on the oral microbiome on systemic and neuroinflammation remains a significant yet largely unexplored gap. This dissertation investigates the hypothesis that cocaine-specifically enriched oral Streptococcus parasanguinis triggers neuroinflammation, neuropathology, and cognitive deficits. In a human study, the saliva microbiomes from chronic cocaine users exhibited reduced α-diversity, enriched Streptococcus genus, …