Species-Specific Discrimination Of Bacterial Biofilms Using A Ratiometric Fluorescence Sensor Array And Machine Learning,
2025
University of Nebraska Medical Center
Species-Specific Discrimination Of Bacterial Biofilms Using A Ratiometric Fluorescence Sensor Array And Machine Learning, Ritika Gupta, Aayushi Laliwala, Elena Muldiiarova, Kenneth W. Bayles, Denis Svechkarev, Marat Sadykov, Aaron M. Mohs
Journal Articles: Pathology and Microbiology
Biofilms are intricate bacterial communities encased in a self-produced extracellular matrix (ECM) of DNA, lipids, proteins, and polysaccharides. The diverse ECM composition across bacterial species significantly influences the progression of biofilm-associated infections, making precise identification crucial for effective treatment. Traditional methods such as biochemical assays, MALDI-TOF mass spectrometry, DNA sequencing and culturing provide valuable insights but have notable drawbacks, including time-consuming procedures, high costs, and the need for specialized equipment and trained personnel. These limitations hinder the rapid and widespread adoption of biofilm identification in clinical settings, underscoring the need for more streamlined, accurate, and accessible methods. In this study, …
Staphylococcus Aureus Encodes Four Differentially Regulated Pyruvate Transporters,
2025
University of Nebraska Medical Center
Staphylococcus Aureus Encodes Four Differentially Regulated Pyruvate Transporters, Jennifer L. Endres, Cleofes Sarmiento, William Xiao, Marat R. Sadykov, Kenneth W. Bayles, Mckenzie K. Lehman
Journal Articles: Pathology and Microbiology
The success of Staphylococcus aureus as a pathogen is attributable, in part, to its ability to exploit the diverse nutrient sources available during infection. Critical to this success are the pathways involving pyruvate that serve as a nexus for energy production, oxidative metabolism, and biosynthetic processes. When available, bacteria acquire pyruvate from the environment to fuel growth. Recently, LrgAB was identified as a pyruvate transporter under microaerobic conditions, leading us to speculate that S. aureus encodes other pyruvate transporters that are active during aerobic growth. In this study, we used the toxic pyruvate analog, 3-fluoropyruvic acid (3-FP), to isolate mutants …
Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates,
2025
University of Kentucky
Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates, Ethan G. Napier, Isaac R. Cinco, Sheridan B. Wagner, Ethan V. Stuart, Qi Qiao, Joshua Taylor, Brian Stevenson, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 …
Evaluation Of Leptospirosis Vaccine Efficacy After Modifications Of N-Linked Glycosylation In Liga Mrna Vaccines.,
2025
Graduate School
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 …
The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates,
2025
Georgia Southern University
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 …
Chronic Alcohol Consumption Induces Phenotypic And Functional Alterations Consistent With A Hyper-Inflammatory State In Peripheral Blood Mononuclear Cell-Derived Microglia In A Rhesus Macaque Model,
2025
University of Kentucky
Chronic Alcohol Consumption Induces Phenotypic And Functional Alterations Consistent With A Hyper-Inflammatory State In Peripheral Blood Mononuclear Cell-Derived Microglia In A Rhesus Macaque Model, Hami Hemati, Madison B. Blanton, Heather E. True, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from rhesus macaque (RM) into induced microglia-like cells (RM-iMGLs). The RM-iMGLs displayed transcriptional profiles distinct from monocyte progenitors and closely resembling primary microglia. Notably, morphological features showed that differentiated RM-iMGLs derived from subjects with chronic alcohol consumption (CAC), while bigger, exhibited a bipolar-like morphology. Additionally, dysregulation in key inflammatory and regulatory markers, along with increased baseline …
Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi,
2025
University of Kentucky
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 …
The Characterization Of Il-27 Production And Its Impact On T Cell Antigen-Specificity And Diversity In A Neonatal Bcg Vaccination Model,
2025
West Virginia University
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 …
Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy,
2025
Oregon National Primate Research Center
Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy, Casey M. Mcguire, Isaac R. Cinco, Diana Takahashi, Kristin A. Sauter, Melissa Kirigiti, Ilhem Messaoudi, Jonah B. Sacha, Charles T. Roberts, Paul Kievit
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean …
Intracellular Survival Of Staphylococcus Aureus In Macrophages During Osteomyelitis,
2025
University of Kentucky
Intracellular Survival Of Staphylococcus Aureus In Macrophages During Osteomyelitis, William A. Lathram, Christopher D. Radka
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies – including biofilm formation, small colony variants, and inhibition of phagolysosomal killing – further enhance persistence and immune evasion. While these …
Identification Of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (Ars),
2025
University of Nebraska Medical Center
Identification Of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (Ars), Kia T. Liermann-Wooldrik, Arpita Chatterjee, Elizabeth A. Kosmacek, Molly Myers, Oluwaseun Adebisi, Louise Monga-Wells, Liu Mei, Michelle P. Takacs, Patrick H. Dussault, Daniel R. Draney, Robert Powers, James W. Checco, Chittibabu Guda, Tomáš Helikar, David B. Berkowitz, Kenneth W. Bayles, Alan H. Epstein, Lynnette Cary, Daryl J. Murry, Rebecca E. Oberley-Deegan
Journal Articles: Pathology and Microbiology
Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro …
Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii,
2025
University of Central Florida
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 Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development,
2025
The Texas Medical Center Library
The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh
Faculty, Staff and Students Publications
Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …
Blood Culture Utilization: How Many Follow-Up Cultures Are Needed?,
2025
Macon & Joan Brock Virginia Health Sciences at Old Dominion University
Blood Culture Utilization: How Many Follow-Up Cultures Are Needed?, George Jones, Jennifer Hanrahan
Department of Medicine Faculty Publications
Background: Follow-up blood cultures (BCx) are ordered after an initial positive culture in many instances. The number of follow-up cultures needed is not clear. Obtaining unnecessary BCx may cause unintended consequences. The optimal balance between stewardship and patient safety warrants investigation. We sought to assess the frequency with which a third set is positive after a negative second BCx. Methods: We conducted a retrospective study of BCx submitted to the microbiology laboratory from 1/1/18-11/1/23. We included all patients ≥18 years who had at least two follow-up BCx drawn 24-72 hours after an initial positive culture. Data were collected from electronic …
The Effect Of Hypochlorous Acid On Cultured Osteoblast And Escherichia Coli,
2025
Missouri State University
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 …
Alcohol-Induced Gut Microbial Reorganization And Associated Overproduction Of Phenylacetylglutamine Promotes Cardiovascular Disease,
2024
Cedars-Sinai Medical Center, Los Angeles, CA
Alcohol-Induced Gut Microbial Reorganization And Associated Overproduction Of Phenylacetylglutamine Promotes Cardiovascular Disease, Zhen Li, Min Gu, Aline Zaparte, Xiaoming Fu, Kala Mahen, Marko Mrdjen, Xinmin S. Li, Zhihong Yang, Jing Ma, Themis Thoudam, Kristina Chandler, Maggie Hesler, Laura Heathers, Kiersten Gorse, Thanh Trung Van, David Wong, Aaron M. Gibson, Zeneng Wang, Christopher M. Taylor, Pearl Quijada, Catherine A. Makarewich, Stanley L. Hazen, Suthat Liangpunsakul, J Mark Brown, David J. Lefer, David A. Welsh, Thomas E. Sharp
School of Medicine Faculty Publications
The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes …
Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice,
2024
The Texas Medical Center Library
Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Jessica R Watts, Jennifer L Spencer Clinton, Jeroen Pollet, Rongsheng Peng, Jie Tan, Paul D Ling
Faculty, Staff and Students Publications
Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily …
Uba1 Inhibition Sensitizes Cancer Cells To Parp Inhibitors,
2024
The Texas Medical Center Library
Uba1 Inhibition Sensitizes Cancer Cells To Parp Inhibitors, Sharad Awasthi, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Yang Li, Sima Khazaei, Sumanta Ghosh, Collene R Jeter, Jinsong Liu, Gordon B Mills, Shannon N Westin, Michael T Lewis, Weiyi Peng, Anil K Sood, Timothy A Yap, S Stephen Yi, Daniel J Mcgrail, Nidhi Sahni
Faculty, Staff and Students Publications
Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells. We show that silencing or pharmacological inhibition of UBA1 sensitizes multiple cell lines and organoid models to PARPi. Mechanistic studies uncover that UBA1 inhibition not only impedes HR repair to sensitize cells to PARP inhibition …
Development Of A Ripk1 Degrader To Enhance Antitumor Immunity,
2024
The Texas Medical Center Library
Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang
Faculty, Staff and Students Publications
The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …
5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines,
2024
University of Mary Washington
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 …
