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Nucleotide-Derived Bacterial Alarmones Attenuate The Induction Of Type-I Interferon Responses In A Murine Macrophage Reporter Cell Line, Ryan P. Kilduff, Erin B. Purcell, Lisa M. Shollenberger

Chemistry & Biochemistry Faculty Publications

The stringent response is a well-studied phenomenon in many bacterial systems and regulates resource-consuming activities such as transcription, translation, and replication. The stringent response is a well-conserved signaling framework, as are the nucleotide-derived signaling mediators, collectively referred to as (p)ppGpp or as alarmones. There is a wealth of research evaluating nucleotide-derived alarmone signaling in bacterial models, however, their potential to modulate innate immune signaling has not yet been evaluated. Several common pathogen-synthesized molecules, such as lipopolysaccharide (LPS) and cyclic-di-AMP (c-di-AMP), act as pathogen-associated molecular patterns (PAMPs), which are common patterns that alert the innate immune system of bacterial infection. The …

Impacts Of Tick Parasitism On The Rodent Gut Microbiome, Robert J. Brinkerhoff, Joshua Pandian, Meghan Leber, Isabella D. Hauser, Holly D. Gaff

Biological Sciences Faculty Publications

Host microbiota may impact disease vector behavior and pathogen transmission, but little is known about associations between ectoparasites and microbial communities in wildlife reservoir species. We used Illumina metagenomic sequencing to explore the impacts of tick parasitism on the rodent fecal microbiome in both a field and laboratory setting. We found that tick parasitism on wild hosts was associated with variation in the fecal microbiota of both the white-footed deermouse, Peromyscus leucopus, and the southern cotton rat, Sigmodon hispidus. In a lab experiment, we detected significant changes to the fecal microbiome after experimental exposure to immature ticks in …

A Novel Silver-Ruthenium-Based Antimicrobial Kills Gram-Negative Bacteria Through Oxidative Stress-Induced Macromolecular Damage, Patrick O. Tawiah

Theses and Dissertations

The rise in drug-resistant bacteria, together with the decline in antibiotic development, requires new strategies for infectious disease control. Gram-negative pathogens are particularly challenging to combat due to their outer membrane. This study highlights the effectiveness of the silver-containing antimicrobial AGXX® against the Gram-negative bacterium Escherichia coli. AGXX® is a promising silver coating that presumably kills bacteria through the generation of reactive oxygen species (ROS). However, neither AGXX®’s mode of action is fully understood, nor have its effects on Gram-negative bacteria or bacterial response and defense mechanisms towards AGXX® been studied in detail. Here, I report that the bactericidal …

Investigating Antimicrobial Efficacy Of Turmeric And Rosemary Oil Against Staphylococcus Aureus, Aishwarya Tripathi

Selected Full-Text Master Theses 2021-

This study investigates the antimicrobial efficacy of turmeric (Curcuma longa) and rosemary essential oil (Rosmarinus officinalis) against Streptococcus aureus, with a comparative analysis to phenoxyethanol, a widely used synthetic preservative. The growing consumer demand for natural cosmetic formulations have intensified the search for plant-derived alternatives to synthetic preservatives. Turmeric and rosemary oil were selected based on their documented antimicrobial, antioxidant, and anti-inflammatory properties. The objective of this research was to evaluate whether these natural agents can serve as effective preservatives in topical gel formulations, either individually or in combination, and how their efficacy compares to phenoxyethanol.

Eight gel-based formulations were …

Deciphering Genetic Contributions To Antibiotic Persistence: Insights From Multi-Gene Knockout Studies, Elise K. Schweer

Electronic Theses and Dissertations

Antibiotic resistance is a critical global health challenge, complicating efforts to treat bacterial infections effectively. Antibiotic persistence plays a significant role in driving resistance. Persisters are a subpopulation of non-dividing bacterial cells that often evade lethal antibiotic treatment. Once antibiotics are removed, these cells "resurrect," resuming growth and may lead to relapsing infections. Notably, the progeny of persister cells exhibit a heightened tendency to acquire mutations or incorporate antibiotic resistance genes, further compounding the challenge of antibiotic resistance. In our recent study, we knocked out seven hypothetical genes and observed a significant reduction in persister levels. Compared to the wild …

Characterization Of Novel Hantaviruses In Paraguay, Ifebuche Nnamani

Theses and Dissertations (ETD)

The genus Orthohantavirus, is a group of tripartite, negative-sense RNA viruses of which some members are the etiologic agents for hemorrhagic fever with renal syndrome (HFRS) or orthohantavirus cardiopulmonary syndrome (HCPS) in the Old and New Worlds, respectively. Sampling of wild rodents for these viruses has increased our knowledge of their host range and continues to lead to the discovery of new orthohantaviruses species and strains. HFRS and HPS have case fatality rates of up to 15% and 40%, respectively. And in some years, morbidity rates of up to 100,000 cases can be reached, globally. The epidemiological evidence of human-to-human …

Elucidation Of The Post-Transcriptional Regulation And Role In Iron Homeostasis Of The Outer Membrane Vesicle Protein Ynce In Salmonella, Mira J. Schmidt

Honors Undergraduate Theses

Iron is an essential element for most bacteria as it is a crucial cofactor for enzymes involved in fundamental reactions such as DNA synthesis. Despite being the fourth most abundant element on Earth, bacteria face challenges acquiring iron under aerobic conditions due to the poor solubility of its oxidized form (Fe³⁺). To overcome this, bacteria have developed various strategies of iron acquisition, such as the production of siderophores. Siderophores are small molecules that scavenge free Fe³⁺ in iron-deprived environments. Iron acquisition is tightly regulated due to its capability of promoting hydrogen peroxide formation via the Fenton reaction. In Salmonella Typhimurium, …

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 …

Schistosoma Mansoni Infection Causes Consistent Changes To The Fecal Bacterial Microbiota Of Mice Across And Within Sites, Mariam A. Mhanna, David T. Gauthier, Lisa M. Shollenberger

Biological Sciences Faculty Publications

Eggs of Schistosoma mansoni are produced by adult female worms in mesenteries of infected hosts. Eggs can cross the intestinal barrier and form granulomas in the tissue or breach and exit the host through fecal excretion. These interactions may affect the host microbiome assemblages. Given the potential for schistosomal alteration of host gut microbiome and subsequent effects on the fecal bacterial composition, it is important to conduct controlled microbiome studies on model animals. While pursuing these studies, it is important to take into account the different conditions in which microbiome studies are conducted and their consequent impacts on variability and …

Molecular Interactions Between The Shellfish Pathogen Vibrio Coralliilyticus Re22 And The Probiont Phaeobacter Inhibens S4sm, Jessica Coppersmith

Open Access Dissertations

Oyster larvae aquaculture is an important industry, both economically and environmentally, helping to create sustainable food systems by supplying seed oysters to farms, and also to restoration projects aimed at building coastal resilience and improving water quality by rejuvenating wild populations. However, oyster larvae are highly susceptible to rapid mortality events, crashes, which can seriously impact the industry. One source of these crashes in hatchery systems is vibriosis, caused by pathogenic species of Vibrio bacteria that are ubiquitous in temperate coastal waters, and with rising surface water temperatures their prevalence and virulence are increasing. To prevent these larval crashes from …

Exploring The Role Of Host Immune Responses And Bacterial Sensory Pathways In The Development Of Treponema Denticola-Mediated Periodontal Disease, Annie N. Hinson

Theses and Dissertations

Periodontitis is a chronic inflammatory disease driven by dysbiotic microbial communities and maladaptive host responses. Treponema denticola, a spirochete pathobiont, is strongly associated with disease severity. However, the molecular mechanisms underlying its interaction with host tissues and regulation of virulence remain incompletely understood. This work examines both the epithelial immune responses and bacterial transduction systems that shape T. denticola pathogenesis. Transcriptomic analysis of gingival keratinocytes revealed IL-36γ as the most highly induced cytokine following infection with T. denticola. Functional studies demonstrated that IL-36γ induction occurs in a dose- and time-dependent manner through TLR2/6 signaling, requiring the NF-κB, PI3K/Akt, and …

Engineering Extracellular Vesicles (Evs) To Combat Infection And Inflammation In Cystic Fibrosis, Sharanya Sarkar

Dartmouth College Ph.D Dissertations

Cystic Fibrosis (CF) is a multisystemic genetic disorder caused by mutations in the CFTR gene, resulting in chronic pulmonary infections, hyperinflammation, and progressive lung damage. Among the pathogens that colonize CF lungs, Pseudomonas aeruginosa (P. aeruginosa) is predominant, infecting over 50% of adults with CF and developing antibiotic resistance over time. Current modulator therapies fail to address persistent bacterial infections, chronic inflammation, or irreversible lung damage, underscoring the need for novel therapeutic strategies. In our previous in vitro studies, we demonstrated that extracellular vesicles (EVs) secreted by primary Human Bronchial Epithelial Cells (HBECs) inhibit P. aeruginosa growth by reducing the …

Role Of Coronavirus Envelope Protein On Infectivity, Garrett E. Zaagman

Dissertations

Coronaviruses infect a wide range of hosts and have caused recent human pandemics. While much has been learned, gaps remain in understanding viral assembly and egress, particularly the role of the envelope (E) protein in specific infectivity. To study this, recombinant MHV viruses were created with E gene deletions and HiBiT-tagged spike (S) proteins to monitor virion release. In mouse cells, MHV∆E S-HiBiT secreted less spike and fewer infectious particles, indicating reduced specific infectivity. Comparisons between human HeLa-CEACAM and mouse DBT cells showed species-specific support for virus production. TMED10, a host membrane protein, was tested as a potential E-interacting partner …

Investigation Of Multiple Factors Influencing The Vector-Borne Transmission Of Salmonella Typhimurium Via Blattella Germanica, Landen Sean Van Hulzen

Dissertations and Theses

The German cockroach (Blattella germanica) is a common urban pest that lives ubiquitously in human structures around the world. German cockroaches are a severe public health threat as they are known carriers and vectors of human pathogens including Salmonella enterica, Escherichia coli, Shigella spp, and more. German cockroach infestations have been associated with Salmonellosis outbreaks. While mechanical transmission by the German cockroach vector is well known, new research suggests that more nuanced biological transmission has a role in maintaining and transmitting Salmonella enterica serovar Typhimurium (S. Typhimurium). Despite this recent finding, many biological variables influencing vector-borne transmission of S. Typhimurium …

The Effects Of Salinity On The Cutaneous Microbiome And Pathogen Infection On The Pacific Tree Frog (Pseudacris Regilla) In Monterey Bay, California, Usa, Hannah Eunhae Kim

EWU Masters Thesis Collection

Global climate change and infectious diseases are considered a leading cause of amphibian population declines worldwide. Changes in precipitation and salinity have altered watershed systems and microbial communities, reducing habitat availability and physiological performances for amphibian survival. The salt refuge hypothesis, however, is a proposed explanation that higher saline environments may reduce susceptibility to pathogens such as Batrachochytrium dendrobatidis (Bd). The Moro Cojo Slough State Marine Reserve (MCSSMR) (California, USA) is known as an abundant breeding ground for endangered/threatened amphibian species. To test and expand the salt refuge hypothesis, I evaluated Bd prevalence and intensity and the cutaneous microbiome of …

Multisociety Guidance For Infection Prevention And Control In Nursing Homes, Lona Mody, Sonali D. Advani, Muhammad Salman Ashraf, Allison H. Bartlett, Suzanne F. Bradley, Deborah P. Burdsall, Jennifer A. Hanrahan, Susan S. Huang, Robert L.P. Jump, Lindsay Nicolle, Mary-Claire Roghmann, Patricia Stone, Rekha K. Murthy

Department of Medicine Faculty Publications

This multisociety guidance was endorsed by SHEA, APIC, IDSA, PALTmed, and AGS. It provides recommendations for infection prevention and control (IPC) in the context of the complexity of nursing home care in the United States: increased medical acuity of residents, the spread of multidrug-resistant organisms, and the threat of emerging pathogens. Recommendations and implementation suggestions address IPC leadership, staffing, and resources, healthcare personnel and residents‘ adherence to precautions and effective hand hygiene, outbreak preparedness, training, occupational health, cleaning and disinfection in the care environment, and the involvement of IPC in the facility. The guidance also addresses the challenges of maintaining …

Evaluation And Identification Of Novel Viruses In Wild Fishes Using Varied Molecular Biology Techniques, Clayton Douglas Raines

Graduate Theses, Dissertations, and Problem Reports (ETD)

Viruses are among the most abundant biological entities on Earth, yet their diversity and ecological roles in aquatic vertebrates, particularly fishes, remain poorly characterized. This dissertation advances fish virology through integrative approaches that combine historical context, molecular diagnostics, and genomic discovery. A novel hepadnavirus (ApHBV) was identified in asymptomatic Alosa pseudoharengus, emphasizing the prevalence of subclinical infections in migratory forage species. In Catostomus commersonii, transcriptomic profiling revealed sexually dimorphic immune responses to hepatitis B and C-like viruses, highlighting complex host-pathogen dynamics. In Micropterus nigricans, next-generation sequencing uncovered a novel nackednavirus and multiple adomaviruses within hyperpigmented lesions, expanding …

Analysis Of The Microbiome Of Amblyomma Americanum In The Statesboro Region, Ella Zierdt, Lorenza Beati, Mary Humphrey, Saviour Dralabu

Honors College Theses

The lone star tick, Amblyomma americanum, is the most common tick in Georgia. It is mainly known as an Ehrlichia spp. vector, but its microbiome can be diverse, depending on geography, developmental stage, and season. Little is known about bacterial diversity in ticks from the southeastern U.S. A Nanopore MinION sequencer was used for a preliminary analysis of the bacterial microbiome in A. americanum from the Statesboro region. DNA was extracted from 39 nymphs, 35 males, and 39 females. DNA samples were pooled by month of collection and life stage/sex, amplified with barcoded 16SrDNA primers, and sequenced. Approx. 77% …

Antibody-Induced Multicellular Behaviors Of Salmonella Typhimurium, Samantha K. Lindberg

Electronic Theses & Dissertations (2024 - present)

Salmonella enterica is a globally distributed bacterial pathogen that is commonly acquired through consumption of contaminated food and water. The enterica subspecies includes over 1500 unique subvariants, or serovars, that are classified by antigen presentation. Due to its global environmental prevalence, broad host range, and increasing pathogenicity, serovar Typhimurium is of particular concern for human and animal health, as well as food safety. Once in the gastrointestinal tract, Salmonella Typhimurium (STm) exploits host immune mechanisms, implements an arsenal of virulence factors, and outcompetes the microbiota to invade the intestinal epithelium. While STm infections are generally self-limiting and relatively mild, emerging …

Cultures For Acid-Fast Bacilli: Are We Being Good Stewards?, Jennifer Hanrahan, Julie D. Sill, Patricia Ver Schneider, Jessica F. Copeland, Elsie Frimpongmaa Amoako-Kissi, Ogochukwu O. Ilobi, Angela J. Toepp

Department of Medicine Faculty Publications

Objective: To describe the use of cultures for acid-fast bacilli (AFB) and situations in which AFB cultures are unlikely to be of clinical benefit.

Design: Retrospective descriptive study of AFB cultures submitted to Sentara Health microbiology laboratory from December 1, 2021, to December 1, 2023. Data were collected from the electronic medical record and included patient demographics, the service line that ordered the culture, specimen source, and culture results.

Setting: Sentara Healthcare System.

Patients: All patients who had specimens submitted to the microbiology laboratory during the study period were included.

Results: A total of 13,944 AFB cultures from 8,243 …

Degradation Of Cyanobacteria And Microalgae Using Ultraviolet Radiation At 222 Nm And Its Application In The Bleaching Of Lampenflora On Cave Rock Surfaces, Keisuke Naito, Shuji Watanabe, Masuo Komukai, Takehiro Kazama, Masayuki Itoh, Masahiro Kawasaki

International Journal of Speleology

Cyanobacterial and microalgae blooms negatively affect ecological environments. One of the emerging problems of these blooms occurs in calcareous caves, where visible lighting systems in tourist caves induce the formation of photosynthetic biofilms known as lampenflora on rock surfaces. In this study, we evaluated the inactivation effect of ultraviolet (UV) light irradiation at 222 nm (rare gas halide lamp) and 254 nm (mercury lamp) on cyanobacteria and microalgae in a laboratory and on lampenflora in Ryusenshindo Cave in Japan. Based on the laboratory experiments, irradiation at 222-nm was more effective than that at 254-nm for degrading plants. The photosensitivity of …

Interactions Of The Sars-Cov-2 Viral Genome 3’-Untranslated Region With Viral And Host Rnas, Caleb Frye, Mihaela Rita Mihailescu

Electronic Theses and Dissertations

This dissertation focuses on the characterization of RNA-RNA interactions within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and with host microRNAs. As the causative agent of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has evolved rapidly since its appearance. This has warranted prompt characterization of the virus particularly of its single stranded RNA (ssRNA) genome. By using a combination of bioinformatics, biophysics, and/or biological assays, we analyzed the SARS-CoV-2 viral genomic RNA and uncovered interactions of genomic RNA with host RNAs, highlighting an underutilized method of targeting RNA viruses. We showed here that the conserved elements in the viral genomic …

Characterizing The Francisella Tularensis Universal Stress Protein, Benjamin Girardo

Theses & Dissertations

Francisella tularensis is an extremely virulent pathogen responsible for the zoonotic disease tularemia. F. tularensis employs various defense mechanisms to survive and persist under diverse environmental and host-induced stress conditions. Despite its significance, the full spectrum of stress factors that enable F. tularensis persistence remain inadequately understood. In many bacterial species, universal stress proteins (Usp) play a crucial role in managing adverse conditions. The aim of this study was to elucidate the role of Usp in F. tularensis as a means of clarifying the stress response mechanisms of this pathogen. The F. tularensis Usp is encoded by a single, highly …

An In-Depth Investigation Into Yersinia Pestis Phages: Isolating A Yersinia Pestis Phage From Soil And Constructing A Comprehensive Phylogenetic Analysis Of Known Yersinia Pestis Phages, Jacqueline Chavez

All HCAS Student Capstones, Theses, and Dissertations

Yersinia pestis, the causative agent of the plague, has become increasingly resistant to many antibiotics; therefore, alternatives such as phage therapy are necessary. Phage therapy uses combinations of bacteriophages or phages, which are viruses that only infect bacteria. However, phages—especially Y. pestis phages —are severely understudied. Thus, this research has sought to specifically isolate a phage from soil that infects Y. pestis. There were 146 samples that were collected from across the US, focusing on those with reported cases of plague. These samples were enriched with Y. pestis to maximize the amount of potential phage that target Y. pestis. …

Differential Responses Of Human Neutrophils To Legionella Species., Hannah E. Hanford

Electronic Theses and Dissertations

Legionella species are Gram-negative facultative intracellular bacterial pathogens commonly found in freshwater or soil environments where they survive and replicate within their natural protozoan hosts. Humans serve as an accidental host for Legionella species after inhalation of contaminated aerosolized water droplets or soil particles enabling the bacteria to enter the lungs, infect alveolar macrophages, and result in severe pneumonia. Evasion of degradation and proliferation within alveolar macrophages by Legionella species and manifestation of “Legionnaires’ disease” is dependent on the Dot/Icm type IV secretion system (T4SS). The T4SS apparatus is a needle-like channel for translocation of over ~350 effector proteins, depending …

Evaluating The Duckweeds Lemna Minor And Spirodela Polyrhiza As Alternative Aquatic Hosts For The Spread Of The Bacterial Wilt Pathogen, Ralstonia Solanacearum, Irelynn Smith

Honors Theses

Ralstonia solanacearum is a plant pathogen that causes bacterial wilt disease in major crops such as tomatoes and potatoes. Recently, this bacterium was discovered in floating pennywort (Hydrocotyle ranunculoides) and Pennsylvania smartweed (Polygonum pennysylvanicum), two previously unsuspected aquatic plants. Duckweed is an aquatic plant with a high level of resilience and short doubling time. Common duckweed (Lemna minor) has previously demonstrated its capability as a versatile high-yield infection model for other types of pathogenic bacteria. Given this newfound branch of aquatic hosts and the fact that duckweed is a common pond weed previously identified in several ponds located nearby infected …

From Resistance To Host Response: An Integrative Study Of C. Difficile Infections, Amber Consul

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides difficile infection (CDI) is a major healthcare challenge, causing severe gastrointestinal illness and significant mortality. Understanding the mechanisms of antibiotic resistance, epidemiology, and immune response in CDI is critical for developing effective treatments and prevention strategies.

This dissertation encompasses three complementary studies. The first study investigates the genetic mechanisms underlying cephalosporin resistance in C. difficile strain 630 through differential gene expression analysis. The second study provides a descriptive epidemiological analysis of C. difficile ribotypes in a Las Vegas patient population, highlighting differences between healthcare-associated (HA-CDI) and community-associated (CA-CDI) cases. The third study integrates serum analyte profiling and transcriptomic analysis …

Lack Of Inflammatory Response In Mouse Embryonic Cells To Listeria Infection, Damilola Oyebode

Master's Theses

Approximately 1 in 5 pregnancies in the United States results in miscarriage, with a significant percentage of these losses attributed to failed implantation due to immunological challenges encountered by the early embryo. Recent research has shown that key cell types within mouse blastocysts, including embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), exhibit remarkable resilience against the cytotoxic effects associated with viral infections and embryotoxic cytokines, such as TNFα and IFNγ, both of which are known to hinder blastocyst development. However, the immune properties of the preimplantation stage embryo, specifically the blastocyst, remain poorly understood. Using mouse cell model, …

Implementing The Methodology To Generate Diagnostic And Therapeutic Antibodies, Andrea Mariana Carlin

Open Access Theses & Dissertations

This research aimed to establish the methodology for developing monoclonal antibodies at The University of Texas at El Paso. Monoclonal antibodies are indispensable across multiple fields, including diagnostics, therapeutics, and biotechnology, yet there is a shortage of commercially available antibodies targeting specific proteins or possessing specialized characteristics. To address this gap, three models were selected: a peptide derived from the intracellular protein Schlafen 8 and two cell surface protein receptors: mouse vascular endothelial growth factor receptor 2 (VEGFR2) and human melanocortin receptor 4 (MC4R). These proteins present unique challenges in antibody generation, including issues of accessibility, expression, and specificity.

Throughout …

Enhancement Of Zika Virus Infection By West Nile And Dengue Virus Antibody Positive Cord-Blood Samples From Mothers In El Paso-Texas, Jeanette Orbegozo

Open Access Theses & Dissertations

The recent Zika virus (ZIKV) outbreak and its association with microcephaly cases and other neurological syndromes are important public health concerns. A phenomenon known as antibody-dependent enhancement (ADE) involves preexisting flavivirus antibodies to a specific flavivirus that enhances the severity of a second infection with a different flavivirus. Since ZIKV is related to flaviviruses like West Nile virus (WNV) and dengue virus (DENV), prior exposure to these viruses could elicit cross-reactive antibodies that may enhance a subsequent ZIKV infection. Therefore, this study aimed to determine if WNV and DENV antibodies from cord blood enhanced ZIKV infection in vitro. Initially, a …