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Uncovering The Mechanisms Underlying The Immunogenicity Of Adenovirus Vaccine Vectors, Natalie Nidetz

Dissertations

Vaccination is historically the most effective tool for preventing infectious disease but current vaccine strategies fail to generate robust immunity to major infectious diseases such as HIV and malaria. Therefore, newer vaccine approaches are needed. Vaccines generated from viral, adenovirus based, vectors (AdVs) have proven highly immunogenic in multiple disease models. However, the clinical use of many AdVs is limited by the presence of pre-existing antibodies in human populations, which prevent expression of antigenic genes during immunization with AdVs based on common adenovirus (Ad) serotypes, such as HAdV-5C. Immunization with rare serotype based AdVs, such as HAdV-28D, are not affected …

Surveying Host Innate Immune Responses To Interferon Antagonist-Deficient Murine Coronaviruses, Aaron Brian Volk

Master's Theses

Two coronaviruses (CoVs)—severe acute respiratory syndrome (SARS) virus and Middle East respiratory syndrome (MERS) virus—have emerged in the 21st century from animal reservoirs into the human population, each causing an epidemic associated with significant disease and mortality. CoV epidemics are currently only controllable by rigorous public health measures; no targeted therapeutics or vaccines exist to treat or prevent any human CoV infection. One method of generating attenuated CoV strains to be studied as vaccine candidates involves specifically disrupting CoV-encoded interferon (IFN) antagonists, thereby rendering the virus vulnerable to host innate antiviral immunity. Deubiquitinating (DUB) activity encoded within CoV nonstructural protein …

Characterizing Immune Response To Hiv-1 Infection In Bicd2-Knockout Cells, Omar Abdel-Rahim

Master's Theses

An important part of the HIV-1 infection cycle is the attachment of the intracellular viral core to the host microtubule network, facilitated by attachment of the viral capsid to cargo adaptor proteins. One such cargo adaptor is Bicaudal D Homolog Protein 2 (BICD2). BICD2 can attach to both the HIV-1 capsid and the dynein/dynactin complex and facilitate the trafficking of the viral core towards the host nucleus. Removal of BICD2 can disrupt this viral translocation, resulting in an elevated immune response that impairs productive HIV-1 infection. In my research, we investigated what viral particles are detected in the absence of …

Production Of Monoclonal Antibodies Against Interferon Gamma Of Asian Elephant Elephas Maximus For Tuberculosis Diagnosis In Elephants By Interferon Gamma Release Assay, Songkiat Songthammanuphap

Chulalongkorn University Theses and Dissertations (Chula ETD)

Tuberculosis is a zoonotic disease that can be transmitted from infected animals to humans. Wild animals such as elephants and non-human primate have been reported to be infected by M. tuberculosis (MTB) complex, which can cause tuberculosis in animals as well. The common TB diagnostic approaches in human such as chest X-ray and tuberculin skin test are not practical in the elephants. Moreover, the gold standard of the bacteria culture from trunk wash has low sensitivity, is time-consuming and can only detect tuberculosis in the active stage. Therefore, an accurate diagnosis covering all phases of the MTB infection is in …

Waterborne Disease Reduction Using Evidence-Based Microbiology Verification In Lower Nyakach, Kenya, Richard R. Blodgett

Walden Dissertations and Doctoral Studies

Waterborne diseases continue to plague the poorest people in low-income countries and are estimated to cause 4,600,000 acute incidents of diarrhea resulting in over 2,000 deaths daily. A major challenge is performing microbiology tests to monitor drinking water quality. Friends of the Old (FOTO) implemented a novel strategy using evidence-based microbiology to educate communities about the relationship between contaminated water and disease. Two commercially available tests for E.coli, adapted for fieldwork, provided easily interpreted results of contamination that correlate with WHO's disease risk categories. Simple and effective household water treatment options 'solar pasteurization and/or chlorination' were provided to all 14,400 …

The Impact Of Lemongrass, Oregano, And Thyme Essential Oils On Candida Albicans' Virulence Factors, Jennifer Marie Eddins

Walden Dissertations and Doctoral Studies

Increased systemic infections and growing resistance of Candida species in immunosuppressed people have prompted research for additional treatment options. The purpose of this quantitative study was to investigate the potential of lemongrass, oregano, and thyme essential oils tested individually, combined, and combined with the antifungal agents fluconazole and caspofungin to kill Candida albicans isolates in a controlled laboratory setting. This study was grounded on the theoretical concepts of the epidemiologic triangle model. The experimental data collected were used to investigate risk factors related to age, gender, race, and comorbidities. Kill rates of lemongrass, oregano, and thyme essential oils individually and …

Clostridium Difficile Infection (Cdi): Use Of Preventive Bundle To Decrease Cdi Incidences, Lisa Feliciano

Walden Dissertations and Doctoral Studies

The challenge of combating Clostridium difficile infections (CDI) is a major problem within many health care organizations as CDI adds to the cost of care and is an uncomfortable and sometimes fatal complication of hospitalization for the patient. The practice-focused question for this doctoral project was targeted at patients in hospital settings on a medical surgical floor and asked if clostridium difficile preventive bundles reduce the incidence of CDI compared with nonstandardized preventative methods. Using the plan-do-study-act framework, the purpose of this DNP project was to use a clostridium difficile bundle approach to study the effects of clostridium difficile incidence …

Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine

Theses and Dissertations (Comprehensive)

Riparian wetlands are unique habitats facilitating all forms of life. The riverbanks of these environments provide ideal conditions for bacteria, plants, and higher organisms. Of particular interest to this research was the variation in microbial community structure at high, intermediate and poor water quality impacted areas. Assessing the capabilities of plants to retain microbial pathogens was identified. Root systems and corresponding soil are ideal locations for bacterial deposition, resulting in attachment at these areas. Biofilm production in these regions is important for long-term establishment, leading to persistence and potential naturalization. Opportunistic pathogens originating from mammalian fecal matter are introduced into …

Indian Research Output In Immunology And Microbiology 2012-2016: A Scientometric Study, Jyoti Rana Ph.D. Scholar, Rakesh Kumar Bhatt Associate Professor

Library Philosophy and Practice (e-journal)

Background: The study examines India’s research productivity in immunology and microbiology during 2012-2016, depending on various parameters, including India’s annual average research growth rate, institutional output profile of institutions and profiles of some of the most productive authors.

Aim: The focus of this study is to analyze performance of India’s research output in immunology and microbiology, the quality and productivity of major institutions participating in research in microbiology and immunology and the productivity and quality of leading authors in research in immunology and microbiology.

Methods: The study in the area of immunology and microbiology using 5 years publications data from …

Molecular Candidates For Blocking The Transmission Of Vector-Borne Diseases, Ashish Naresh Vora

Biological Sciences Theses & Dissertations

Vector-borne diseases (VBDs) require urgent attention as they have a high mortality rate, with 700,000 people dying in a year as of 2017. So far, extremely few reliable vaccination strategies and solutions have emerged. Transmission blocking vaccines are one among many solutions available to manage the control of VBDs. These require identification of both vector and pathogen molecules that play important roles in the transmission, dissemination and establishment of VBDs. Our strategy is to characterize these candidates that play important roles in vector-host-pathogen interactions. This manuscript presents two such studies identifying the participation of two arthropod molecules in vector-host-pathogen interactions. …

Mutational Analysis Of The Molluscum Contagiosum Virus Mc160 Protein, Henri Estanbouli

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum Contagiosum Virus (MCV), belongs to a family of large DNA viruses called Poxviridae. MCV causes a common skin infection resulting in benign neoplasms. 122 million cases of MC were reported in 2010. The virus is not primarily lethal, though fatalities have occurred due to secondary bacterial infections. Even with the high volume of reported cases, MCV is very much understudied, and its pathogenicity is not well understood. Thus, with that in mind, a more in-depth understanding of the MCV-host interactions is a priority. Presumably during infection, MCV utilizes immune evasion molecules to inhibit activation of the host pro-inflammatory …

Changing Antimalarial Drug Sensitivities In Uganda, Stephanie Alexis Rasmussen

Dissertations, Masters Theses, Capstones, and Culminating Projects

Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of …

Human Metapneumovirus Induces Formation Of Inclusion Bodies For Efficient Genome Replication And Transcription, Nicolás P. Cifuentes-Muñoz, Jean Branttie, Kerri Beth Slaughter, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA …

Vibrio Vulnificus Monitoring Along The Coastal Bend And The Rio Grande Valley, Texas, Louay Bachnak

Honors Theses

Vibrio vulnificus is a common opportunistic pathogen found in marine, coastal, and estuarine waters. This one micrometer microorganism is the leading cause of deaths in the United States due to food poisoning after consumption of raw or undercooked seafood. The optimal temperature for survival is between 15.6°C and 35.0°C with moderate salinities – conditions frequently found in the Gulf of Mexico (Lin, Payne, & Schwarz, 2003).

In the United States, V. vulnificus infections are more common in states bordering the Gulf of Mexico, including Texas. However, infections can still occur in individuals consuming infected food more inland or sustain wounds …

Type Ix Secretion System: Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Comparing The Effectiveness Of Alternative And Prescription Antibiotics Against Gram-Positive Bacteria, Rachel Jenkins, Roan Dickenson, Sam Turnbull, Marcela Torres

Senior Theses

The rapid emergence of antibiotic-resistant bacteria is a global public health concern that threatens the efficacy of antibiotic drugs. We found that natural remedies, specifically coconut oil, honey and cinnamon essential oil, have the potential to be used as a clinical alternative to treat antibiotic-resistant infections. In this experiment, we performed a disk diffusion test and measured the area of inhibition of each treatment to compare the effectiveness of natural and prescription antibiotics. Cinnamon essential oil showed significantly greater antibiotic activity compared to a prescription treatment, amoxicillin. With bacterial resistance continuously expanding, more work needs to be done to determine …

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity …

Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham

Dissertations and Theses (Open Access)

The human microbiome is a diverse polymicrobial population comprised of both fungi and bacteria. Perturbations of the normal microbiome can have a profound impact on health, including the development of infections. Exploitation of these polymicrobial interactions has the potential to provide novel treatment and prevention strategies for infectious diseases. Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also amongst the most important and problematic, opportunistic nosocomial pathogens and are often co-isolated during infection. Surprisingly, these two species antagonize each other’s …

Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone

Graduate Theses and Dissertations

Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry respective …

Development Of A Broadly Protective Modified-Live Virus Vaccine Candidate Against Porcine Reproductive And Respiratory Syndrome Virus, Haiyan Sun, Aspen Workman, Fernando A. Osorio, David J. Steffen, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

Modified-live virus (MLV) vaccines are widely used to protect pigs against porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV vaccines do not confer adequate levels of heterologous protection, presumably due to the substantial genetic diversity of PRRSV isolates circulating in the field. To overcome this genetic variation challenge, we recently generated a synthetic PRRSV strain containing a consensus genomic sequence of PRRSV-2. We demonstrated that our synthetic PRRSV strain confers unprecedented levels of heterologous protection. However, the synthetic PRRSV strain at passage 1 (hereafter designated CON-P1) is highly virulent and therefore, is not suitable to be used as …

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …

Efficacy Of An Adenoviral Vectored Multivalent Centralized Influenza Vaccine, Amy Lingel, Brianna L. Bullard, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010–2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10–100 MLD50 of H1N1, H3N1, H3N2 and H5N1 influenza viruses. The traditional vaccines induced robust levels of HA inhibition (HI) titers, but failed to protect against five different heterologous lethal influenza challenges. Conversely, the multivalent consensus vaccine (1 × 1010 virus particles (vp)/mouse) induced protective HI titers of ≥40 against 8 of 10 influenza viruses that represent a wide degree of divergence within …

The Ecology Of Antibiotic Resistance: Sources And Persistence Of Vancomycin-Resistant Enterococci And Antibiotic Resistant Genes In Aquatic Environments, Suzanne M. Young

USF Tampa Graduate Theses and Dissertations

The growing crisis of antibiotic resistance is a major threat to ecosystems and human health. Infections caused by known and emerging antibiotic resistant pathogens are on the rise globally, with approximately 700,000 deaths per year caused by antibiotic resistant bacteria (1). In the United States, infections from antibiotic resistant bacteria cause more than 2 million illnesses and 23,000 deaths (2). Antibiotic resistant bacteria and antibiotic resistance genes are released into aquatic ecosystems through hospital waste, residential sewer lines and animal agricultural waste streams. Animal agriculture accounts for approximately 70% of antibiotic use in the United States (3). In agricultural ecosystems, …

Emergence Of The L Phenotype In Group B Streptococci In The South Of Ireland, Katherine Hayes, Lesley Cotter, L. Barry, Fiona O'Halloran

Department of Biological Sciences Publications

Group B Streptococcal isolates (n = 235) from the South of Ireland were characterised by serotyping, antimicrobial susceptibility and determination of the phenotypic and genotypic mechanisms of resistance. Resistance to erythromycin and clindamycin was observed in 21·3% and 20·4% of the total population, respectively. The c-MLSB phenotype was the most common phenotype detected (62%), with ermB being the predominant genetic determinant, present in 84% of resistant isolates. The rare L phenotype was observed in 2·9% (n = 7) of isolates, four of which harboured the lsaC gene responsible for clindamycin resistance. Serotypes Ia, III and II were the most common …

Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton

USF Tampa Graduate Theses and Dissertations

The emergence and proliferation of Gram-negative bacteria expressing β-lactamases is a significant threat to human health. β-Lactamases are enzymes that degrade the β-lactam antibiotics (e.g., penicillins, cephalosporins, monobactams, and carbapenems) that we use to treat a diverse range of bacterial infections. Specifically, β-lactamases catalyze a hydrolysis reaction where the β-lactam ring common to all β-lactam antibiotics and responsible for their antibacterial activity, is opened, leaving an inactive drug. There are two groups of β-lactamases: serine enzymes that use an active site serine residue for β-lactam hydrolysis and metalloenzymes that use either one or two zinc ions for catalysis. Serine enzymes …

Susceptibility Pattern Of Methicillin Resistant Staphylococcus Aureus To Vancomycin And Other Alternate Agents: Report From A Private Sector Hospital Laboratory, Faryal Saleem, Naima Fasih, Afia Zafar

Department of Pathology and Laboratory Medicine

With increasing prevalence of methicillin resistant Staphylococcus aureus in clinical settings and injudicious use of antibiotics, resistance among MRSA against commonly used antibiotics is increasing. To assess the susceptibility pattern of MRSA against vancomycin, linezolid, tigecycline, rifampicin, fosfomycin fusidic acid, clindamycin, trimethoprim-sulfamethoxazole and teicoplanin, minimum inhibitory concentrations (MICs) for given antimicrobials were performed on 234 MRSA clinical isolates using automated VITEK 2 system. Vancomycin, linezolid, rifampicin, clindamycin, co-trimoxazole and teicoplanin susceptibilities were interpreted according to CLSI breakpoints, while tigecycline, fosfomycin and fusidic acid were interpreted according to BSAC breakpoints. All isolates were found susceptible to vancomycin, tigecycline, teicoplanin and linezolid. …

Susceptibility Pattern Of Methicillin Resistant Staphylococcus Aureus To Vancomycin And Other Alternate Agents: Report From A Private Sector Hospital Laboratory, Faryal Saleem, Naima Fasih, Afia Zafar

Department of Pathology and Laboratory Medicine

With increasing prevalence of methicillin resistant Staphylococcus aureus in clinical settings and injudicious use of antibiotics, resistance among MRSA against commonly used antibiotics is increasing. To assess the susceptibility pattern of MRSA against vancomycin, linezolid, tigecycline, rifampicin, fosfomycin fusidic acid, clindamycin, trimethoprim-sulfamethoxazole and teicoplanin, minimum inhibitory concentrations (MICs) for given antimicrobials were performed on 234 MRSA clinical isolates using automated VITEK 2 system. Vancomycin, linezolid, rifampicin, clindamycin, cotrimoxazole and teicoplanin susceptibilities were interpreted according to CLSI breakpoints, while tigecycline, fosfomycin and fusidic acid were interpreted according to BSAC breakpoints. All isolates were found susceptible to ancomycin, tigecycline, teicoplanin and linezolid. …

High-Throughput Single-Molecule Telomere Characterization, Jennifer Mccaffrey, Eleanor Young, Katy Lassahn, Justin Sibert, Steven Pastor, Harold Riethman, Ming Xiao

School of Medical Diagnostics & Translational Sciences Publications

We have developed a novel method that enables global subtelomere and haplotype-resolved analysis of telomere lengths at the single-molecule level. An in vitro CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human (TTAGGG) n DNA tracts in genomes that have also been barcoded using a separate nickase enzyme that recognizes a 7bp motif genome-wide. High-throughput imaging and analysis of large DNA single molecules from genomes labeled in this fashion using a nanochannel array system permits mapping through subtelomere repeat element (SRE) regions to unique chromosomal DNA while simultaneously measuring the (TTAGGG) n tract length at the end of each …

Is Tb Testing Associated With Increased Blood Interferon-Gamma Levels?, Aideen E. Kennedy, Jim O'Mahony, Noel Byrne, John Macsharry, Riona G. Sayers

Department of Biological Sciences Publications

The Republic of Ireland reports a relatively low prevalence of Johne’s disease (JD) compared to international counterparts. Postulated reasons for this include a lower average herd size and a grass-based production system. Ireland also engages in high levels of bovine tuberculosis (bTB) testing. As interferon-gamma (IFN-γ) is believed to play a key role in protecting against JD, it is our hypothesis that administration of purified protein derivative (PPD), as part of the bTB test, is associated with a systemic increase in IFN-γ production, which may potentially limit clinical progression of the disease. We studied 265 cows (202 Friesian and 63 …

Differential Roles For Inner Membrane Complex Proteins Across Toxoplasma Gondii And Sarcocystis Neurona Development, Rashmi Dubey, Brooke Harrison, Sriveny Dangoudoubiyam, Giulia Bandini, Katherine Cheng, Aziz Kosber, Carolina Agop-Nersesian, Daniel K. Howe, John Samuelson, David J. P. Ferguson, Marc-Jan Gubbels

Maxwell H. Gluck Equine Research Center Faculty Publications

The inner membrane complex (IMC) of apicomplexan parasites contains a network of intermediate filament-like proteins. The 14 alveolin domain-containing IMC proteins in Toxoplasma gondii fall into different groups defined by their distinct spatiotemporal dynamics during the internal budding process of tachyzoites. Here, we analyzed representatives of different IMC protein groups across all stages of the Toxoplasma life cycle and during Sarcocystis neurona asexual development. We found that across asexually dividing Toxoplasma stages, IMC7 is present exclusively in the mother’s cytoskeleton, whereas IMC1 and IMC3 are both present in mother and daughter cytoskeletons (IMC3 is strongly enriched in daughter buds). In …