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Articles 1 - 20 of 20
Full-Text Articles in Pathogenic Microbiology
The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou
The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou
Doctoral Dissertations
Candida albicans phosphatidylserine (PS) synthase, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals against systemic candidiasis due to its importance in virulence, absence in the host and conservation among fungal pathogens. This dissertation is focused on the identification of inhibitors for this membrane enzyme. Cho1 has two substrates: cytidyldiphosphate-diacylglycerol (CDP-DAG) and serine. Previous studies identified a conserved CDP-alcohol phosphotransferase (CAPT) binding motif present within Cho1, and here we revealed that mutations in all but one conserved amino acid within the CAPT motif resulted in decreased Cho1. For serine, we have predicted a …
A Biochemical Approach To Characterize A Divergent Trypanosoma Brucei Mitochondrial Dna Polymerase, Polib, Stephanie B. Delzell
A Biochemical Approach To Characterize A Divergent Trypanosoma Brucei Mitochondrial Dna Polymerase, Polib, Stephanie B. Delzell
Doctoral Dissertations
Trypanosoma brucei is a single-celled parasitic protist that causes African sleeping sickness in people and nagana in cattle in sub-Saharan Africa. T. brucei and related trypanosomatid parasites contain an unusual catenated mitochondrial genome known as kinetoplast DNA (kDNA) composed of dozens of 23 kb maxicircles and thousands of 1 kb minicircles. The kDNA structure and replication mechanism are divergent from other eukaryotes and essential for parasite survival. POLIB is one of three Family A DNA polymerases that are independently essential to maintain the kDNA network, and has been implicated in minicircle replication. However, the division of labor among the paralogs, …
Induction And Evasion Of Neutrophil Extracellular Traps By Campylobacter Jejuni And Its Implication In Disease, Sean M. Callahan
Induction And Evasion Of Neutrophil Extracellular Traps By Campylobacter Jejuni And Its Implication In Disease, Sean M. Callahan
Doctoral Dissertations
Campylobacteriosis, the foodborne disease caused by Campylobacter spp., infects one out of 10 individuals every year. C. jejuni accounts for 90% of these infections resulting in numerous postinfectious disorders including the development of colorectal cancer, Guillain-Barré syndrome, irritable bowel syndrome, and reactive arthritis. Despite its large impact on human health, the host immune response to the bacterium is largely uncharacterized. Chapter two of this dissertation addresses the development of neutrophil extracellular traps (NETs) within human and ferret campylobacteriosis. We observed NET-associated proteins increase in the feces of C. jejuni-infected patients and that in vitro C. jejuni induces NETs, which …
Cat Covid, Cmv And Chemokines, Oh My!, Trevor Hancock
Cat Covid, Cmv And Chemokines, Oh My!, Trevor Hancock
Doctoral Dissertations
Cytomegalovirus (CMV) is an important pathogen infecting most humans worldwide. CMV infection within immunocompromised individuals can cause severe morbidity and potential mortality. Disease during CMV infection is due to virus dissemination and subsequent inflammation. Host immune cells lie at the intersection potentially mediating both. The CMV-encoded viral chemokine vCXCL-1 is a proposed virulence factor in mouse models increasing immune cell recruitment and disease. However, the primary immune cell mediator is undetermined. To identify targets, Chapter 2 examines CXCR2 expression (receptor for vCXCL-1) among various mouse tissues and human peripheral blood under steady-state conditions. In vitro, isoforms of HCMV’s vCXCL-1 …
Mechanisms By Which Xenorhabdus Nematophila Interacts With Hosts Using Integrated -Omics Approaches, Nicholas C. Mucci
Mechanisms By Which Xenorhabdus Nematophila Interacts With Hosts Using Integrated -Omics Approaches, Nicholas C. Mucci
Doctoral Dissertations
Nearly all organisms exist in proximity to microbes. These microbes perform most of the essential metabolic processes necessary for homeostasis, forming the nearly hidden support system of Earth. Microbial symbiosis, which is defined as the long-term physical association between host and microbes, relies on communication between the microbial community and their host organism. These interactions among higher order organisms (such as animals, plants, and fungi) and their bacteria links metabolic processes between interkingdom consortia. Many questions on microbial behavior within a host remain poorly understood, such as the colonization efficiency among different microbial species, or how environmental context changes their …
Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis
Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis
Doctoral Dissertations
Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability …
Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados
Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados
Doctoral Dissertations
DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. These processes are coordinated to maintain genome integrity and ensure accurate duplication of genetic and epigenetic information. Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. In this study, we adapted …
Studies On The P. Aeruginosa T3s Translocon Assembly: Interaction Of Popd With Membranes, Yuzhou Tang
Studies On The P. Aeruginosa T3s Translocon Assembly: Interaction Of Popd With Membranes, Yuzhou Tang
Doctoral Dissertations
Type III secretion (T3S) system is deployed by a wide range of pathogens to manipulate host cell response and establish infection. The T3S system is a syringe-like apparatus that spans across the double membrane of bacteria, protruding 50nm-80nm into the extracellular space and connecting with target cell membrane. In Pseudomonas aeruginosa, the proteins PopB and PopD are secreted and found associated with the target eukaryotic cell membrane. These two proteins are believed to form a transmembrane complex or translocon to allow effector protein translocation. Despite its key role in pathogenesis, the assembly mechanism and structure of this critical transmembrane …
The Role Of The Metallochaperone Hypa In The Acid Survival And Activities Of Nickel Enzymes In Helicobacter Pylori, Heidi Hu
Doctoral Dissertations
Helicobacter pylori is a bacterium that has colonized the human gastric mucosa of over 50% of the world population. Persistent infection can cause gastritis, peptic ulcers, and cancers. The ability of H. pylori to colonize the acidic environment of the human stomach is dependent on the activity of the nickel containing enzymes, urease and NiFe-hydrogenase. The nickel metallochaperone, HypA, was previously shown to be required for the full activity of both enzymes. In addition to a Ni-binding site, HypA also contains a structural Zn site, which has been characterized to alter its averaged structure depending on pH and the presence …
Colicins - A Sound Antimicrobial Approach For The Prevention Of Catheter-Associated Urinary Tract Infections, Sandra M. Roy
Colicins - A Sound Antimicrobial Approach For The Prevention Of Catheter-Associated Urinary Tract Infections, Sandra M. Roy
Doctoral Dissertations
The emergence and spread of antibiotic resistance has created one of the greatest challenges in fighting infectious disease. We address the rise of antibiotic-resistant pathogens by examining the evolutionary history of a class of resistance determinants, the SHV b-lactamases. We isolated the genes that encode the SHV beta-lactamases (blaSHV genes) from clinical settings and from an environment essentially devoid of antibiotic use. Our data suggests that, counter to current dogma, the use of antibiotics in the clinic is not creating these resistance genes; genes for antibiotic resistance already exist in nature and our use of antibiotics in clinical …
Multilayered Regulation Of The Type I Toxin Zoro In Ehec, Jia Wen
Multilayered Regulation Of The Type I Toxin Zoro In Ehec, Jia Wen
Doctoral Dissertations
A bacterial type I toxin-antitoxin system contains two genes: one encodes a small toxic protein and the second, a small regulatory RNA (sRNA) that inhibits toxin production. To date, very few type I loci have been described thoroughly in regards to the regulation of toxin and the function of the toxin at endogenous levels. In this study, I demonstrated that the zor-orz locus of Escherichia coli O157:H7 is composed of two highly homologous type I toxin-antitoxin systems: zorO-orzO and zorP-orzP. The zor genes encode the toxins and the orz genes encode the antitoxin sRNAs. Overexpression of zorO is toxic …
Novel Advancements For Improving Sprout Safety, Kyle S. Landry
Novel Advancements For Improving Sprout Safety, Kyle S. Landry
Doctoral Dissertations
All varieties of bean sprouts (mung bean, alfalfa, broccoli, and radish) are classified as a “super-food” and are common staples for health conscious consumers. Along with the proposed health benefits, there is also an inherent risk of foodborne illness. When sprouts are cooked, there is little risk of illness. The purpose of this dissertation was to explore novel techniques to minimize or prevent the incidence of foodborne illness associated with the consumption of sprouts. Three areas were investigated: 1) the use of a biocontrol organism, 2) the use of a novel spontaneous carvacrol nanoemulsion, and 3) the influence of the …
The Role Of Phosphatidylserine And Phosphatidylethanolamine In Candida Albicans Virulence, Sarah Elizabeth Davis
The Role Of Phosphatidylserine And Phosphatidylethanolamine In Candida Albicans Virulence, Sarah Elizabeth Davis
Doctoral Dissertations
In hospitalized patients with neutropenia, Candida albicans is the fourth leading cause of systemic bloodstream infections, which have a mortality rate of approximately 30 %. The phosphatidylserine synthase enzyme of C. albicans, Cho1p, appears to be a good drug target as a mutant lacking this enzyme (the cho1Δ/Δ [null mutant]) is avirulent in animal models of Candida infections and this enzyme is not conserved in humans. We discovered that the loss of phosphatidylserine (PS) synthesis affects C. albicans' expression of the Als3p adhesin, a virulence protein, and loss of PS synthesis also compromises the cell wall, causing increased …
Genetic Diversity, Population Structure, And Evolution Of Virulence In Toxoplasma Gondii, Elliot Keats Cullen Shwab
Genetic Diversity, Population Structure, And Evolution Of Virulence In Toxoplasma Gondii, Elliot Keats Cullen Shwab
Doctoral Dissertations
Toxoplasma gondii is among the most widespread eukaryotic pathogens known. It chronically infects approximately one third of the world’s human population and has been isolated from an extremely diverse array of globally distributed mammals and birds. Understanding the structure of the worldwide T. gondii population enhances our understanding of the factors that have shaped that structure and led to the proliferation of one of the most evolutionarily successful pathogens on Earth. Herein we collate genotypic data from global isolates, demonstrating that T. gondii possesses a unique population structure in which only a small number of genotypes dominate throughout the northern …
Thermal Inactivation Of Shiga Toxin-Producing Escherichia Coli In Foods, Malcond David Valladares
Thermal Inactivation Of Shiga Toxin-Producing Escherichia Coli In Foods, Malcond David Valladares
Doctoral Dissertations
Emerging non-O157 Shiga toxin-producing Escherichia coli (STEC) were recently added to the zero tolerance policy by the USDA-FSIS. Therefore, the precise characterization of their thermal inactivation kinetics in different foods and the effect of stress on thermal inactivation are needed. This research aimed at determining the heat inactivation kinetics of non-O157 and O157 STECs in buffer and model food matrices and the effects of DnaK levels on thermal resistance after acid and heat-shock. Thermal inactivation was carried out in either in 2-ml glass vials or nylon vacuum-sealed bags for buffer and food (spinach, ground-beef, turkey deli-meat, pasta) samples, respectively. Vials …
Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood
Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood
Doctoral Dissertations
Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …
Efficacy Of Biopesticides For Organic Management Of Cucumber Beetles, Mary A. Rogers
Efficacy Of Biopesticides For Organic Management Of Cucumber Beetles, Mary A. Rogers
Doctoral Dissertations
Organic growers are limited in crop protection techniques for cucumber beetle management. Spotted (Diabrotica undecimpunctata howardi) and striped (Acalymma vitatta) cucumber beetles and are significant pests of cucurbits in the U.S. Feeding results in aesthetic damage and reduction in marketable yields as well as transmission of bacterial wilt that can result in plant mortality. Biopesticides are products formulated from naturally occurring organisms such as fungi and bacteria that are pathogenic or toxic to insect pests. Advantages to these products are that they have low environmental risk, low risk to non-target organisms including mammals and beneficial insects, …
Investigation Of Host Responses Upon Infection Of Distinct Toxoplasma Strains, Rachel Devonne Hill
Investigation Of Host Responses Upon Infection Of Distinct Toxoplasma Strains, Rachel Devonne Hill
Doctoral Dissertations
Toxoplasma gondii is the causative agent of Toxoplasmosis in human and animals. T. gondii isolates are highly diverse. Hundreds of genotypes have been identified, but only three clonal lineages, namely Type I, II and III are prevalent worldwide. In mouse model, T. gondii strains can be divided into three groups based on their virulence, including the virulent (LD100=1), the intermediately virulent (LD50 = 103-104) and the non virulent (LD50 > 105). The clonal Type I, II and III T. gondii strains belong to these three groups, respectively. Epidemiologic studies suggest the …
Methicillin Resistance In Staphylococcus Pseudintermedius, Chad Christopher Black
Methicillin Resistance In Staphylococcus Pseudintermedius, Chad Christopher Black
Doctoral Dissertations
Staphylococcus pseudintermedius affecting dogs is analogous to S. aureus on humans, acting as both normal flora and opportunistic pathogen. Methicillin resistance in S. pseudintermedius is recent, with the first documented occurrence of an isolate bearing the methicillin resistance gene, mecA, in 1999. This gene encodes penicillin binding protein 2a, which renders all beta-lactam drugs ineffective and functions as a “gateway” antibiotic resistance determinant. In the presence of ineffective antibiotics, opportunities for mutational events and acquisition of mobile genetic elements increase as microbial densities increase, often leading to multi-drug resistance. Methicillin-resistant S. pseudintermedius (MRSP) infections have become increasingly common. For …
Campylobacter Pathogenesis And Subunit Vaccine Development, Ximin Zeng
Campylobacter Pathogenesis And Subunit Vaccine Development, Ximin Zeng
Doctoral Dissertations
Campylobacter jejuni is the leading bacterial cause of human gastroenteritis in the United States. Increasing resistance of Campylobacter to clinical antibiotics raises an urgent need for novel strategies to prevent and control infections in humans and animal reservoirs, which necessitates a better understanding of Campylobacter pathogenesis. We hypothesize that multidrug efflux pump CmeABC and ferric enterobactin (FeEnt) iron acquisition systems, which play a critical role in Campylobacter pathogenesis, are novel targets for developing effective measures against Campylobacter. To test this, the molecular, antigenic, functional, and protective characteristics of two outer membrane proteins, CmeC (an essential component of CmeABC drug efflux …