Comprehensive Investigation Into The Molecular Mechanisms Driving The Emergence Of Emm4 Group A Streptococcus, Chioma Odo, Samuel A Shelburne, Anthony R. Flores, Steven J Norris, Anna Konovalova, Blake Hanson

Dissertations and Theses (Open Access)

Abstract

Comprehensive Investigation into the Molecular Mechanisms Driving the Emergence of emm4 Group A Streptococcus

Chioma Modeline Odo, M.S.

Advisory Professor: Samuel A. Shelburne, MD, Ph.D.

The major gram-positive bacterium group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it is well known to cause infections that occur in waves. GAS strains are grouped based on the composition of the N-terminal sequence of the M protein which is encoded by the emm gene. With the advent of large-scale whole genome sequencing, GAS clonal emergence events in emm1, emm3, and emm89 types have been identified …

Assessment Of Tce And Chiral Pcb Dechlorination Rate, Congener Diversity, And Enantioselectivity In Town Creek, Sc, Usa Sediment Microcosms, Catherine P. Sumner

All Dissertations

Polychlorinated biphenyls (PCBs) and trichloroethene (TCE) are ubiquitous contaminants and are recognized as persistent organic pollutants due to their extreme chemical stability. PCBs were manufactured by chlorinating biphenyls that created 209 congeners with various structures, of which 19 are chiral and can exist as a pair of stable atropisomers. PCBs have been known to cause developmental and neurological toxicity in humans and wildlife; they can act as endocrine disrupters, carcinogens, and teratogens. Sangamo Weston Inc. was an industrial plant located near Town Creek in Pickens Country, South Carolina, that manufactured capacitors and used Aroclors 1016 and 1254 as dialectic fluids …

The Impact Of Reactive Oxygen Species On Bactericidal Activity And Drug Resistance In Salmonella Typhimurium Upon Chlorine And Eugenol Exposure, Mohammed Aljuwayd

Graduate Theses and Dissertations

Salmonella Typhimurium (S.T) is a foodborne pathogenic bacterium which causes salmonellosis in human beings. Chicken is the most common source of S.T contamination. In chapter I, I discuss the growth of the poultry industry, the role chickens play as Salmonella reservoirs, the spread of drug-resistant strains caused by chicken husbandry and antibiotic use, and how eugenol can be used in poultry feed to decrease Salmonella infections and improve intestinal health. In chapter Ⅱ, I summarize the role of reactive oxygen species (ROS) in bactericidal activity. In chapter Ⅲ, I describe the killing mechanism of sodium hypochlorite (NaOCl) and identify the …

Candida Albicans Farnesol Synthesis And Secretion, Daniel J. Gutzmann

School of Biological Sciences: Dissertations, Theses, and Student Research

Candida albicans is a polymorphic fungus and opportunistic commensal found primarily in the gastrointestinal and skin of healthy individuals. Several barriers prevent C. albicans from causing disease including a healthy immune system and microbiome. When these barriers become comprised, C. albicans can transition to a pathogen and disseminate through the intestinal mucosa leading to life-threatening bloodstream and invasive infections with mortality rates of up to 64%. Morphogenic plasticity is key to this transition and impacts virulence, adaptation to different host environments, and evasion of host immune responses. One regulator of morphogenesis is farnesol. Farnesol is a secondary metabolite of …

Characterizing Enterobacter Cloacae Genetic Elements Responsible For Interactions With Candida Albicans, Abigail Suarez

Electronic Theses and Dissertations

Polymicrobial interactions are an important, yet understudied area of research. Candida albicans is the most common human fungal pathogen. The bacterial genus, Enterobacter, is a source of nosocomial acquired infections and increased drug resistance. Our lab has previously discovered that Enterobacter preferentially adheres to C. albicans hyphae. From an E. cloacae transposon library screen, six candidates displayed reduction in C. albicans attachment. These candidates were identified genetically and characterized for involvement in attachment to C. albicans. A fluorescent plasmid was introduced into E. cloacae to measure and observe adherence to C. albicans in planktonic and biofilm growth. In vivo …

Phylogenomic Analyses Of Three Distinct Lineages Uniting Staphylococcus Cohnii Snd Staphylococcus Urealyticus From Diverse Hosts, L. Caroline House, Amer Hasan, Andi Asnayanti, Adnan A. Alrubaye, Jeff Pummill, Douglas Rhoads

Poultry Science Faculty Publications and Presentations

We sequenced and assembled genomes for 17 isolates of Staphylococcus cohnii isolated from osteomyelitis lesions in young broilers from two separate experiments where we induced lameness using a hybrid wire-litter flooring system. Whole genome comparisons using three different methods support a close relationship of genomes from both S. cohnii and Staphylococcus urealyticus. The data support three different lineages, which we designated as Lineage 1, Lineage 2, and Lineage 3, uniting these two species within an evolving complex. We present evidence for horizontal transfer between lineages of genomic regions from 50–440 kbp. The transfer of a 186 kbp region from …

Evaluating The Impact Of The Poultrystar®Bro Probiotic On The Incidence Of Bacterial Chondronecrosis With Osteomyelitis Using The Aerosol Transmission Challenge Model, Ruvindu Perera, Khawla Alharbi, Amer Hasan, Andi Asnayanti, Anh Dang Trieu Do, Abdulkarim Shwani, Raj Murugesan, Shelby Ramirez, Michael Kidd, Adnan A. Alrubaye

Poultry Science Faculty Publications and Presentations

Bacterial chondronecrosis with osteomyelitis (BCO) lameness is a major welfare issue for broiler production worldwide affecting approximately 1.5% of broilers over 42 days old. Excessive body weight gain causes mechanical stress on long bones, leading to micro-fractures. This condition induces a bacterial infection of fractures, resulting in bone necrosis and eventual BCO lameness. Increasing gut integrity and supporting Calcium metabolism contribute to the optimal bone structure and subsequently reduce BCO lameness. Probiotics thus provide an excellent strategy for alleviating BCO due to the improvement of intestinal integrity and barrier function. Accordingly, the present study investigated the lameness reduction through the …

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of Helicobacter Pylori, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba

Pathology, East Africa

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …

Candida Albicans Farnesol Synthesis And Secretion, Daniel John Gutzmann

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Candida albicans is a polymorphic fungus and opportunistic commensal found primarily in the gastrointestinal and skin of healthy individuals. Several barriers prevent C. albicans from causing disease including a healthy immune system and microbiome. When these barriers become comprised, C. albicans can transition to a pathogen and disseminate through the intestinal mucosa leading to life-threatening bloodstream and invasive infections with mortality rates of up to 64%. Morphogenic plasticity is key to this transition and impacts virulence, adaptation to different host environments, and evasion of host immune responses. One regulator of morphogenesis is farnesol. Farnesol is a secondary metabolite …

Mechanisms Of Neurodevelopmental Toxicity Of Topiramate, John W Steele, Vaishnav Krishnan, Richard H Finnell

Faculty, Staff and Students Publications

Prescriptions for antiseizure medications (ASMs) have been rapidly growing over the last several decades due, in part, to an expanding list of clinical indications for which they are now prescribed. This trend has raised concern for potential adverse neurodevelopmental outcomes in ASM-exposed pregnancies. Recent large scale population studies have suggested that the use of topiramate (TOPAMAX, Janssen-Cilag), when prescribed for seizure control, migraines, and/or weight management, is associated with an increased risk for autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD) in exposed offspring. Here, we critically review epidemiologic evidence demonstrating the neurobehavioral teratogenicity of topiramate and speculate …

The Interaction Of Endorepellin And Neurexin Triggers Neuroepithelial Autophagy And Maintains Neural Tube Development, Lei Lu, Meizhu Bai, Yufang Zheng, Xiukun Wang, Zhongzhong Chen, Rui Peng, Richard H Finnell, Tongjin Zhao, Chengtao Li, Bo Wu, Yunping Lei, Jinsong Li, Hongyan Wang

Faculty, Staff and Students Publications

Heparan sulfate proteoglycan 2 (HSPG2) gene encodes the matrix protein Perlecan, and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects (NTDs). We discovered rare genetic variants of HSPG2 in 10% cases compared to only 4% in controls among a cohort of 369 NTDs. Endorepellin, a peptide cleaved from the domain V of Perlecan, is known to promote angiogenesis and autophagy in endothelial cells. The roles of enderepellin in neurodevelopment remain unclear so far. Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the …

Antimicrobials Produced By Ants: Chemical Properties And Microbe Specificity, Katy Chon

Master's Theses

Antibiotic resistance is a growing public health concern worldwide, and for over a decade, we have been witnessing the growth of difficult to treat infectious diseases caused by bacteria that are becoming resistant to antibiotics. This resistance can be mostly related to the misusing and improper use of antibiotics in both humans and animals. To restore this problem, humans have turned to new sources for the production of antibiotics. In this study, we focused on using ants. Social insects, including ants and bees, have faced strong disease pressures during their evolution and have developed a range of methods to fight …

Gestational Diabetes As A Risk Factor For Gbs Maternal Rectovaginal Colonization: A Systematic Review And Meta-Analysis, Vicki Mercado-Evans, Jacob J Zulk, Zainab A Hameed, Kathryn A Patras

Faculty, Staff and Students Publications

BACKGROUND: Maternal rectovaginal colonization by group B Streptococcus (GBS) increases the risk of perinatal GBS disease that can lead to death or long-term neurological impairment. Factors that increase the risk of rectovaginal GBS carriage are incompletely understood resulting in missed opportunities for detecting GBS in risk-based clinical approaches. There is a lacking consensus on whether gestational diabetes mellitus (GDM) is a risk factor for rectovaginal GBS. This systematic review and meta-analysis aims to address current conflicting findings and determine whether GDM should be clinically considered as a risk factor for maternal GBS colonization.

METHODS: Peer-reviewed studies that provided GDM prevalence …

Host-Microbiome Interactions In The Teleost Brain, Amir Mani Varnoosfaderani

Biology ETDs

This dissertation investigates host-microbial interactions within the teleost brain, previously considered sterile. Reviewing current literature highlights significant gaps in understanding teleost brain immunity, despite prevalent neurotropic diseases. We mapped the immune profiles of rainbow trout brains and meninges, revealing the olfactory bulbs as the immune effector part of the brain and the optic tectum as a nod2 expression hub. High il6 and il10 levels were noted in the telencephalon. A persistent bacterial community within healthy salmonid brains shares diversity with gut and blood microbiota. Brain bacterial isolates exhibit genomic signatures for brain colonization and polyamine biosynthesis. The microbiota shifts across …

Predation Of Appendicularians On Prochlorococcus, Carey Sweeney

Dissertations and Theses

Prochlorococcus is the most abundant photosynthetic cell on Earth. This picocyanobacterium is critical to primary productivity and biogeochemical cycles of the open ocean. While abiotic environmental factors that influence Prochlorococcus are relatively well-understood, biotic controls are less well known. Appendicularians are ubiquitous gelatinous zooplankton that feed on marine microorganisms including Prochlorococcus. However, the details of this feeding interaction are extremely understudied relative to its potential importance. In this study, I characterized the relationship between appendicularians and Prochlorococcus with laboratory experiments. I showed that feeding on Prochlorococcus changes with the life stage of the appendicularians and concentration of prey. I …

Functional And Structural Analysis Of The Neimann-Pick Disease Type C Pathway To Include Caveolin-1, Anthony Michael Seat

Chemistry and Chemical Biology ETDs

Human disease is often thought of as an all or nothing prospect, either one has the disease or one does not. This does not bear out in clinical or personal experiences, instead demonstrating that disease occurs within a spectrum ranging from presumed unaffected to demonstrably and detrimentally affected.Neimann-Pick disease is one example of this spectrum look into diseased states, with multiple named versions of a phenotypically similar disease. We focus on Neimann-Picktype C (NPC), which is the result of a disruption in the efflux of cholesterol and sphingolipids from the endocytic pathway. NPC demonstrates this concept of a spectrum of …

Full-Length Αiibβ3 Cryo-Em Structure Reveals Intact Integrin Initiate-Activation Intrinsic Architecture, Tong Huo, Hongjiang Wu, Zeinab Moussa, Mehmet Sen, Valerie Dalton, Zhao Wang

Faculty, Staff and Students Publications

Integrin αIIbβ3 is the key receptor regulating platelet retraction and accumulation and a proven drug-target for antithrombotic therapies. Here we resolve the cryoEM structures of the full-length αIIbβ3, which covers three distinct states along the activation pathway. Firstly, we obtain the αIIbβ3 structure at 3Å resolution in the inactive state, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the ligand-binding domain tucked in a specific angle proximity to the TM region. After the addition of a Mn2+ agonist, we resolve two coexisting structures representing two new states between inactive and active state. Our structures show …

Msl2 Variants Lead To A Neurodevelopmental Syndrome With Lack Of Coordination, Epilepsy, Specific Dysmorphisms, And A Distinct Episignature, Remzi Karayol, Maria Carla Borroto, Sadegheh Haghshenas, Anoja Namasivayam, Jack Reilly, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley Mcconkey, Maria Shvedunova, Andrea K Petersen, Kari Magnussen, Christiane Zweier, Georgia Vasileiou, André Reis, Juliann M Savatt, Meghan R Mulligan, Louise S Bicknell, Gemma Poke, Aya Abu-El-Haija, Jessica Duis, Vickie Hannig, Siddharth Srivastava, Elizabeth Barkoudah, Natalie S Hauser, Myrthe Van Den Born, Uri Hamiel, Noa Henig, Hagit Baris Feldman, Shane Mckee, Ingrid P C Krapels, Yunping Lei, Albena Todorova, Ralitsa Yordanova, Slavena Atemin, Mihael Rogac, Vivienne Mcconnell, Anna Chassevent, Kristin W Barañano, Vandana Shashi, Jennifer A Sullivan, Angela Peron, Maria Iascone, Maria P Canevini, Jennifer Friedman, Iris A Reyes, Janell Kierstein, Joseph J Shen, Faria N Ahmed, Xiao Mao, Berta Almoguera, Fiona Blanco-Kelly, Konrad Platzer, Ariana-Berenike Treu, Juliette Quilichini, Alexia Bourgois, Nicolas Chatron, Louis Januel, Christelle Rougeot, Deanna Alexis Carere, Kristin G Monaghan, Justine Rousseau, Kenneth A Myers, Bekim Sadikovic, Asifa Akhtar, Philippe M Campeau

Faculty, Staff and Students Publications

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding …

Novel Antivirals Unveiled Against Acute And Persistent Coxsackievirus B3 Infection Via Rapid Screening, Maria Del Mar Villanueva Guzman

Master's Theses

Enteroviruses cause 10 to 15 million infections annually in the United States, and Coxsackievirus B3 is one of the most commonly reported. Coxsackieviruses may become persistent, characterized as a viral infection that is not cleared from host cells and that generates a continuous infection. Patients who develop persistent CVB3 infection may not respond to the same antivirals as an acute infection, which may be detrimental. Therefore, there is a need for broad-range antiviral drugs to combat acute and persistent CVB3 infection, as there is no well-accepted treatment available. We developed a model system to study persistent CVB3 using a pancreatic …

Novel Antivirals Unveiled Against Acute And Persistent Coxsackievirus B3 Infection Via Rapid Screening, Maria Del Mar Villanueva Guzman

Master's Theses

Enteroviruses cause 10 to 15 million infections annually in the United States, and Coxsackievirus B3 is one of the most commonly reported. Coxsackieviruses may become persistent, characterized as a viral infection that is not cleared from host cells and that generates a continuous infection. Patients who develop persistent CVB3 infection may not respond to the same antivirals as an acute infection, which may be detrimental. Therefore, there is a need for broad-range antiviral drugs to combat acute and persistent CVB3 infection, as there is no well-accepted treatment available. We developed a model system to study persistent CVB3 using a pancreatic …