Medical Microbiology Commons^™

Characterization Of Catechol-Type Siderophore(S) From P. Mosselii Cfml 90-83, Kemper R. Rasnake

Electronic Theses and Dissertations

Iron is essential for many biological processes, where it is used as a cofactor. Even though it is abundant in the Earth’s crust, it is in an insoluble form unavailable to microorganisms in the soil. To overcome this, bacteria produce siderophores, which are secondary metabolites that have a high affinity for iron. This allows bacterial cells to obtain insoluble iron that is essential for survival. Pseudomonas mosselii, a Gram negative bacterium, was isolated from soil. It was selected for further analysis as it was found to produce siderophore(s) under iron-limited conditions, which have not been characterized previously. Therefore, we aimed …

Effects Of “Zero Sugar” Energy Drinks On Microbial Proliferation In Relation To The Gastrointestinal Microbiome, Madison Hines

Honors Theses

Energy drinks have rapidly increased in popularity and availability in recent years. With the rise of high-caffeine beverages, complications due to caffeine consumption have become more common in younger populations. The aim of this study was to use controlled laboratory methods to determine the effect of energy drinks on a variety of organisms commonly found in the gastrointestinal (GI) tract. The diverse and dynamic nature of microbes in the gut makes conditions of the GI tract difficult to replicate in a laboratory setting. As an alternative, isolates of bacteria commonly found as normal flora in the GI tract were plated …

The Role Of Bacteriophage In The Rgg1-Mediated Virulence Control Of Streptococcus Pyogenes, Yuan Tian

Dissertations and Theses

In Streptococcus pyogenes, bacteriophages and other horizontally transmissible elements (HTEs) comprise approximately 10% of the genome, and each clinical isolate carries a unique combination of these elements, contributing to genetic diversity, virulence, antibiotic resistance, and immune evasion. Previously, our laboratory identified binding sites of the transcriptional regulator Rgg1 in the clinical isolate NZ131 and demonstrated that Rgg1 influences genome-wide gene expression, including bacteriophage genes. In the clinical isolate SF370, the prophage SpyCIM1, positioned in the chromosome between the mutL and mutS genes, controls DNA mismatch repair through excision and reintegration into the chromosome. In the integrated form, the prophage displaces …

The Structure, Dynamics, And Impact Of An Interbacterial Weapon Encoded By Human Gut Bacteria, Casey John Latario

Dartmouth College Ph.D Dissertations

The human gut is densely colonized by diverse bacteria. Over a human’s growth, the GI tract becomes a dynamic community that is subjected to a continual in-flow of nutrients and would-be colonizers and an out-flow of microbes and waste products. Despite these dynamics, the bacterial community often displays stability, with particular strains persisting over decades. These stable colonizers have evolved mechanisms to bolster their colonization, resist disruption by other microbes, and persist through environmental flux.

Both interbacterial competition and horizontal gene transfer (HGT) contribute to colonization and survival within the GI tract. A major mechanism for interbacterial competition is the …

Exploring Biopsychosocial Influences On Hookup Culture And Disrupting Compulsory Behaviors In Emerging Adults: A Multidisciplinary Analysis Of A Contemporary Public Health Concern, Catherine Benjamin

Honors Theses and Capstones

Multidisciplinary analysis, including biology, psychology, and sociology, to better understand the compulsory Hookup Culture that exists as a contemporary public health concern among the age group defined as emerging adults. Sexually Transmitted Infections (STIs) diagnoses are steadily rising in the United States and disproportionately affecting college students. Early socialization and current educational resources that contribute to shame and stigma are discussed to explain how lifestyle and social conditions can act as risk factors for individual health outcomes.

Post-Metabolites Of Two Commensal Bacteria Suppress Dna Damage In An Experimental Model Of Acid Reflux Disease, Maanya Pradeep

Honors Undergraduate Theses

Chronic heartburn or gastroesophageal reflux disease (GERD) affects approximately 25% of the US population [1]. Repeated bile acid exposure from the regurgitation of stomach contents leads to the production of reactive oxygen species (ROS), which can cause oxidative DNA damage and promote genomic instability [2]. Barrett’s esophagus (BE), which can develop as a response to chronic bile acid exposure, increases the risk of esophageal adenocarcinoma (EAC) by 30% to 125% [1].

There are more than 18,000 new cases of esophageal cancer in the United States each year, and while its incidence is relatively low compared to other cancers, its mortality …

Green Synthesis Of And Antimicrobial Susceptibility Testing Of (2z)-2-[(4-Fluorophenyl)Methylidene]-1-Benzofuran-3-One, Rod Albert C. Olofernes

Honors Theses

Antimicrobial resistance is a global health challenge, rendering once-effective antibiotics less potent or entirely ineffective. In response, there is increasing interest in developing antimicrobial agents through environmentally sustainable methods. In this study, a fluorinated aurone derivative, (2Z)-2-[(4-fluorophenyl)methylidene]-1-benzofuran-3-one, was synthesized using a green Knoevenagel condensation approach. Eco-friendly catalysts were employed to minimize environmental impact and avoid hazardous byproducts. Product formation was confirmed to avoid wasting resources. The compound was evaluated for antimicrobial properties using a Kirby-Bauer plate, but did not demonstrate consistent or significant antimicrobial activity, therefore lacking promise as a standalone antibiotic.

Enhancing Preparedness: A Genetic Study Of Sar-Cov-2 And Other Microbial Public Health Threats In Wastewater From A College Town, Christian N. Hutchinson

Master's Theses

Problem

The SARS-CoV-2 (COVID-19) pandemic revealed both the systemic vulnerabilities of our healthcare system as well as the importance of timely, localized data for informing public health responses. Traditional testing approaches were essential but often failed to capture the full extent of viral spread, especially in those with mild or asymptomatic conditions that relied on at home testing. This underreporting hindered effective allocation of resources and made developing effective intervention strategies difficult. We also realized the potential for wastewater surveillance to be applied to tracking antimicrobial resistance gene markers. Taken together, this approach should have important implications for improving public …

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

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 …

The Attitudes And Perspectives Of Laboratory Professionals On The Use Of Machine Learning Combined With Maldi For Viral Identification: A Qualitative Study, Grace Johnson

Honors Projects

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with machine learning (ML) has been proposed by numerous studies as a novel approach for viral identification. However, the development and implementation of this instrumentation is still in its early stages, and laboratory professionals' perspectives on its feasibility, accuracy, implementation, and effect on current laboratory operating procedures remain underexplored.

This study aimed to investigate laboratory professionals’ attitudes and opinions regarding the use of MALDI-TOF-MS coupled with machine learning for viral identification, focusing on perceived benefits, barriers, and factors that would affect participants’ opinions on implementation.

A qualitative descriptive research …

In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans

Theses, Dissertations and Capstones

In a 2019 report by the Centers for Disease Control and Prevention (CDC), infections resistant to antibiotic treatment amount to about three million infections and 48,000 deaths. Antimicrobial resistance is an escalating global threat as existing antibiotics lose efficacy over time. The project described is focused on partnering with pharmaceutical researchers and producers to test new nanoparticle-based or repurposed compounds. The central hypothesis of this thesis is that pharmaceutical formulations such as nanoparticles may provide a cost-effective means of combating the emerging antimicrobial resistance. The nanoparticle compounds allowed for a wide range of customization for the pharmaceutical design, since the …

The Effect Of Hypochlorous Acid On Cultured Osteoblast And Escherichia Coli, Cristina Flaquer Fusté

Graduate Theses/Dissertations

Hypochlorous acid (HOCl), a naturally occurring compound in neutrophils, has been used as an antimicrobial in wound treatment. Osteoblasts, bone-forming cells, within the bone tissue play a large role in bone fracture healing. Orthopedic infections are challenging to treat and highly morbid, including surgical site infection of arthroplasty procedures or infection in the setting of compound fractures. HOCl is being considered as a surgical antiseptic to decrease infections in orthopedic surgical procedures. This study therefore seeks to determine the effects of HOCl on osteoblasts and E. coli. Cultured osteoblasts were incubated with varying concentrations of HOCl to examine osteoblast …

The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates, Gabrielle Nascimento

Honors College Theses

In recent decades, cases of community-acquired MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) have been on the rise. The ability of antibiotic resistance to transfer between microorganisms greatly expands its threat to the effective treatment and containment of bacterial infections. The mecA gene is found on a mobile cassette within the Staphylococcal cell and encodes for PBP2a, an alternate version of penicillin-binding protein (PBP) with less binding affinity for β-lactam antibiotics, increasing resistance to the effects of antibiotics. The goal of this research is to investigate the horizontal transfer of the mecA gene between various Staphylococcus species as well as to …

Evaluation Of Leptospirosis Vaccine Efficacy After Modifications Of N-Linked Glycosylation In Liga Mrna Vaccines., Rampapat Phaetthayanan

Chulalongkorn University Theses and Dissertations (Chula ETD)

Leptospirosis, caused by pathogenic Leptospira species, is a widespread zoonotic disease, particularly prevalent in developing countries in tropical areas. Commercially available bacterins have several limitations. A previous study developed a messenger RNA (mRNA) vaccine encoding the carboxy-terminal domain 7-13 of LigA (LigAc) that was expressed with glycosylation in mammalian cells and elicited high humoral immune response in a hamster model but failed to provide protection against lethal challenge. To improve the protective efficacy, this study aimed to develop LigAc-mRNA vaccines with minimal glycosylation. Three mRNA constructs were developed based on two strategies: modifying the potential N-glycosylation sites (from asparagine to …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii, Dimyana Bottros

Honors Undergraduate Theses

Clostridium, a genus of anaerobic, spore-forming bacteria, includes clinically and ecologically significant species like Clostridium difficile and Paeniclostridium sordellii. C. difficile causes antibiotic-associated colitis, while P. sordellii is linked to fatal infections and spontaneous abortions. Recent studies found both species in marine sediments, suggesting their role in environmental and wildlife health disturbances, including the 2013 mass mortality of over 300 manatees in the Indian River Lagoon. However, isolating and differentiating P. sordellii is challenging due to the lack of selective media optimized for its growth. This thesis proposes a novel selective medium tailored to P. sordellii’s physiological …

The Characterization Of Il-27 Production And Its Impact On T Cell Antigen-Specificity And Diversity In A Neonatal Bcg Vaccination Model, Ashley M. Divens

Graduate Theses, Dissertations, and Problem Reports (ETD)

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), and it has plagued humans for most of recorded history. Despite strong efforts to prevent and treat TB, it remains the leading cause of death due to a pathogen and is most prevalent in certain regions of Asia and Africa. Currently, the only approved vaccine to prevent TB is the live-attenuated Bacillus Calmette-Guérin (BCG) vaccine. Most countries have a universal BCG vaccination policy, but the vaccine ultimately fails to be protective. The BCG vaccine is most effective in children and protects against disseminated TB, but protection wanes 10-15 years after vaccination causing …

5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker

Departmental Honors & Graduate Capstone Projects

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …

Elucidating The Mechanism Of Interleukin-17a Signaling In The Pathogenesis Of West Nile Virus, Farzana Nazneen

Dissertations

West Nile Virus (WNV), a neurotropic flavivirus transmitted by mosquitoes, is a leading cause of viral encephalitis in the United States and remains a significant public health concern. Unfortunately, no vaccine or therapeutic intervention is available against WNV infection. Previous studies, including ours, demonstrated that interleukin-17A (IL-17A) signaling increases the cytotoxic potential of CD8⁺ T cells to facilitate WNV and parasite clearance; however, the molecular mechanism is not understood. IL-17 receptor C (IL-17RC) is an obligatory co-receptor with IL-17 receptor A (IL-17RA) for signaling induced by IL-17A, IL-17A/F, and IL-17F. In this study, we found that IL-17RC deficient ( …

The Experience Of Homelessness And Its Effects On Gut Eubiosis, Kamerin Villagomez

University Honors Theses

Microorganisms which populate the human gastrointestinal tract (GIT) have a profound effect on overall human health. The relationship between host health and eubiosis, or balance, of the GIT microbiome is symbiotic and can have reciprocal relationships with quality of sleep, quality of diet, stress and mental health, and the experience of pain. These specific aspects of health are unique in populations experiencing homelessness due to the multi-dimensional and complex nature of their lived experience. Very few studies explore populations experiencing homelessness, with even fewer investigating the intersection between this population and the human GIT microbiome. It is important to do …

Deciphering The Microbial Fingerprint Of Covid-19: A Multi-Layered Exploration Of The Oral And Gut Microbiome Dysbiosis, Iman Mostafa Sultan

Theses and Dissertations

The impact of SARS-CoV-2 infection on the human microbiome remains a dynamic and intricate puzzle. This study delves deeper into this mystery by revisiting the oral and gut microbial compositions of 53 COVID-19 patients before and after viral clearance, alongside comparisons to 76 healthy individuals. Through a comparative lens, we have emploed two distinct differential abundance methods – DeSeq2 and ANCOM – while drawing upon the thorough SILVA database encompassing the full-length 16S rRNA gene. The analysis underscores the crucial role of a diverse methodological choir in microbiome research. In certain instances, the congruence between DeSeq2 and ANCOM may exhibit …

Clonality And Epidemiological Studies Of E. Coli Strain Collected From Abu Dhabi Emirate Using Ngs And Bioinformatic Tools, Ahmed Abdelrahman Mohamed

Theses

In the current landscape, where antibiotic resistance in bacteria is steadily rising, the role of bacterial genomics has assumed increasing significance. Therefore, it is necessary for microbiologists to acquire proficiency in the utilization of these methods and tools to harness their potential in gaining valuable insights into bacterial genomes. This can facilitate the development of innovative strategies for managing and treating bacterial infections. Here we present the power of the whole-genome sequencing technology in characterization of multidrug resistant Escherichia coli isolates. Fourteen Escherichia coli isolates were selected for this study. Following the standard microbiological techniques to confirm the sample identification, …

Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs) have been revolutionary in the fight against cancer by recruiting the host immune system as an agent for attack on malignant cells. Unfortunately, immune-related adverse events (irAEs), including ICI-mediated colitis (IMC), are common side effects that result from immune cell mediated damage on healthy tissues. Recent studies have highlighted a role for the gut microbiota in modulating ICI-mediated anti-tumor responses, but less is known regarding how the gut microbiota may impact on irAEs. Considering that the gastrointestinal tract harbors thousands of unique microbial species, many of which are known to modulate the immune system, microbes and …

Molecular Basis Of Cell Membrane Adaption Against Daptomycin In Enterococcus Faecalis, April Nguyen

Dissertations and Theses (Open Access)

Daptomycin is a last-resort lipopeptide antibiotic that disrupts cell membrane (CM) and peptidoglycan homeostasis (Grein et al., 2020a; Müller et al., 2016a). Enterococcus faecalis has developed a sophisticated mechanism to avoid daptomycin killing by redistributing CM anionic phospholipids away from the septum. The CM changes are orchestrated by a three-component regulatory system, designated LiaFSR, with a possible contribution of cardiolipin synthase (Cls) (Cesar A Arias et al., 2011a; Khan et al., 2019b; Palmer et al., 2011a; Panesso et al., 2015a; Reyes et al., 2015a). However, the mechanism by which LiaFSR controls the cell membrane response and the role of Cls …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

Clostridioides Difficile: Identification Of Rival Organisms & Evaluation Of Non-Antibiotic Treatment Implementation, Justin Davis

Honors Undergraduate Theses

Clostrioides difficile is a common cause of nosocomial (hospital-acquired) infections. Patients receiving antibiotic treatment experience dysbiosis of gut microbiota, and C. difficile, normally held in check by the various other organisms, takes this opportunity to propagate. Symptoms of infection generally include diarrhea, colitis, dehydration, and fever. Understanding that C. difficile generally only causes illness when it is the dominant bacterium (i.e. when growth is relatively unchecked by other microbes), it is appropriate to investigate potential competitive organisms that may be introduced after antibiotic courses or during active C. difficile infection to effectively displace it. Fecal samples from the University …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

Effects Of Stat3 Variant On Stat1 And Stat5b In Fibroblasts From Mice With Stat3 Gain-Of-Function Variant, Natthakan Thareram

Chulalongkorn University Theses and Dissertations (Chula ETD)

STAT mutations cause immune system dysfunction and many diseases, such as autoimmune cytopenias, lymphoproliferative disorders, susceptibility to infections, endocrinopathies, and growth defects. However, the molecular activity of these proteins remains unclear. Here, we investigated the phosphorylation, nuclear translocation, and gene expression levels of Stat1, Stat3, and Stat5b, as well as downstream target genes of these proteins, using mouse fibroblasts with Stat3 wild type and Stat3 L387R gain-of-function (GOF) variant edited by CRISPR-Cas9 technique as a model. In fibroblasts of Stat3 L387R GOF animals, the expression of downstream target genes of STAT1, Cxcl10 and Irf7 were significantly decreased compared with Stat3 …

Advancing Clinical Bacterial Diagnosis: Gram-Stained Whole-Slide Image Classification With Attention-Based Deep Learning, Jack Mcmahon

Computer Science Senior Theses

We introduce a new method for the classification of Gram-stained WSIs. As a test for the diagnosis of blood infections, Gram stains are highly relevant to informing patient treatment. Rapid analysis of Gram stains has been shown to be positively associated with better clinical outcomes, indicating the need for better tools to aid in automatic Gram stain analysis. To date, this area of research has been underexplored, with previous studies relying on the manual patch-level annotation of WSIs to generate training data. This is the first application of a transformer-based model to Gram-stain WSI classification, an approach that is far …