Immunology and Infectious Disease Commons^™

Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe

Department of Biological Sciences Publications

The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …

Why We Still Need To Worry About Bees, Meaghan Lee Callaghan

Capstones

American honey bees, and other native bee species, are still in decline, though the specter of colony collapse disorder may be fading behind us. Colony decline, the loss of bees overwinter experienced across the country at a quarter to third lost per hive (sometimes more), is now expected. Losses can include those from colony collapse disorder. The author discusses the different causes for colony decline and speaks to bee health scientists and local beekeepers. Read more at: http://www.meaghanleecallaghan.com/capstone/index.html

Staphylococcus Aureus Biofilms Interfere With Macrophage Antimicrobial Responses Through Differential Gene Regulation, Toxin Production, And Purine Metabolism, Tyler D. Scherr

Theses & Dissertations

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that is a leading cause of both nosocomial and community-associated infections. Armed with a myriad of virulence factors and the propensity to form a biofilm on native tissues and implanted medical devices alike, S. aureus infections represent a very real public health threat, the treatment of which results in an excessive economic burden. S. aureus biofilm infections are notoriously recalcitrant to antibiotic therapy and adept at evading and neutralizing the host immune antimicrobial response. Previous studies from our laboratory have shown that S. aureus biofilms are able to cause persistent …

Role Of Cbl-Family Ubiquitin Ligases As Critical Negative Regulators Of T Cell Activation And Functions, Benjamin Goetz

Theses & Dissertations

Adaptive T cell immunity is essential for defense against foreign antigens and immune surveillance against cancer. Tight regulation of T cell activation is required to avoid autoimmunity to self-antigens or protracted inflammation after foreign antigens are cleared. Incomplete or inappropriate stimulation leads to an active shutdown of T cell activation called anergy. The Casitas B-lineage Lymphoma (CBL)-family of ubiquitin ligases (E3s) are essential negative regulators of T cell activation that impinge on thymic selection as well as anergy induction programs. Single gene studies show that CBL is critical during T cell development while CBL-B plays an essential role in peripheral …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3%) cases …

Repurposing Non-Antimicrobial Drugs To Treat Multi-Drug Resistant Bacterial And Fungal Infections, Shankar Thangamani

Open Access Dissertations

Bacterial and fungal resistance to conventional antimicrobials is a burgeoning global health epidemic that necessitates urgent action. Even more alarming, the development of new antimicrobials to treat these multidrug-resistant pathogens has not kept pace with the rapid emergence of resistance to current antimicrobials. Antimicrobial drug development through the traditional de novo process is a risky venture given the significant financial and time investment required by researchers and limited success rate of translating these compounds to the clinical setting. This has led researchers to mine existing libraries of clinical molecules in order to repurpose old drugs for new applications (as antimicrobials). …

The Effects Of Dietary Probiotic Inclusion On Skeletal Health Of Poultry And Its Possible Mechanisms, Feifei Yan

Open Access Dissertations

Probiotics are live microorganisms which may confer health benefits on the host when administered in appropriate amounts. Numerous studies have shown that probiotics improve bone health in humans and rodents with less information available on the skeletal health of avians given probiotics. The objective of this study was to determine the effects of probiotic supplementation on bone health of egg-laying and meat-type chickens. Dietary supplementation of a multi-species based probiotic reduced the percentage of shell-less eggs beginning at 4 wk following treatment and increased tibial and femoral bone mineral density in egg-laying hens at 7 wk post-treatment. Similarly, bone mineralization …

Regulation Of Alpha-Herpesvirus Reactivation From Latency By Stress, Insun Kook

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine herpes virus 1 (BHV-1) and Herpes simplex virus 1 (HSV-1) are crucial etiological viral agent of clinical diseases. HSV-1 and BHV-1 establish latent infection in sensory neurons. Periodically, reactivation from latency occurs resulting in virus excretion and transmission. Stress increases corticosteroid levels and the incidence of HSV-1 and BHV-1 reactivation from latency. The synthetic corticosteroid, dexamethasone (DEX) mimics stress and induces BHV-1 and HSV-1 reactivation. However, molecular mechanisms by which corticosteroid mediates viral reactivation are not well understood. My dissertation has focused on elucidating events that induce BHV- 1 or HSV-1 reactivation during the early stages of stress-induced escape …

Nucelotide Substitution Rates In Hantavirus Cd8+ T-Cell Epitopes, Brian Gerald Sikes

Graduate Theses

Hantaviruses pathogenic to humans are exclusive to rodents. Typically each hantavirus is associated with only one host species. Due to their close association, the geographical distributions are the same. Old World species, such as Hantaan hantavirus and Puumala hantavirus, induce symptoms described as the Hemorrhagic Fever with Renal Syndrome (HFRS). The New World hantaviruses, such as Andes hantavirus and Sin Nombre hantavirus, share a suite of symptoms that have been described as Hantavirus Pulmonary Syndrome (HPS). In this study, 16 well-characterized cytotoxic T lymphocytes (CTL) epitopes of the nucleocapsid (N) protein were identified from the literature.

These 16 …

Survey Of Nasal Mites (Acari: Rhinonyssidae, Ereynetidae, Turbinoptidae) In Birds From Three States In The United States, Alexis Danel Hilario Perez

Graduate Theses and Dissertations

Avian nasal mites are obligate endoparasites that spend their entire life in the respiratory system of birds. In North America, bird nasal mites are represented by different unrelated families in three different orders of mites: Rhinonyssidae (Mesostigmata), Ereynetidae (Prostigmata), and the Cytoditidae and Turbinoptidae (Astigmata). The most-diverse and most-abundant family of nasal mites is the Rhinonyssidae, in which mite species may have different levels of host specificity from host orders to families or even species level. Nasal mites in North America have been surveyed in different locations, such as studies ranging from the Gulf Coast of the US to Canada. …

Immunotherapeutic Strategies To Reverse Tumor Associated Immunosuppression In Breast Cancer, Sruthi Ravindranathan

Graduate Theses and Dissertations

Heterogenous cancers such as breast carcinoma, would highly benefit from personalized vaccine approaches such as autologous tumor cell vaccines (ATCVs). By using cancer cells that are isolated from self, this approach has the potential to generate a polyclonal immune response against tumor antigens, that are specific to the individual. However, so far, ATCVs against breast cancers have not had any clinical success due to the poor immunogenicity of the malignant cells.

In this study, for the first time, we determined tumor derived G-CSF to play a major role in affecting immune response against breast cancer ATCVs. By using CRISPR/Cas9 genome …

Phenotypic Analysis And Localization Of Leukocytes At The Site Of Intradermal Injection Of Phytohemagglutinin In Chickens, Kallie Alyce Sullivan

Graduate Theses and Dissertations

Phytohemagglutinin (PHA) is commonly used to gain insight into an individual’s cellular immuno-competence. PHA is typically injected intradermally (i.d.) into the skin (e.g. wing web) and the tissue swelling response is then monitored, whereby the extent of the swelling positively relates to the individual’s cellular immune system capabilities. Although i.d. injected PHA was shown to stimulate mononuclear cell- and basophil-infiltration to the site of injection, reports on temporal, qualitative and quantitative aspects of the local PHA response are limited. The objective of this study was to use the growing feather (GF) as a cutaneous test-site to assess and monitor the …

Diversity And Impacts Of Mining On The Non-Volant Small Mammal Communities Of Two Vegetation Types In The Brazilian Amazon, Natália Carneiro Ardente, Átilla Colombo Ferreguetti, Donald Gettinger, Pricila Leal, Ana Cristina Mendes-Oliveira, Fernanda Martins-Hatano, Helena Godoy Bergallo

Harold W. Manter Laboratory of Parasitology: Faculty Publications

The CarajaÂs National Forest contains some of the largest iron ore deposits in the world. The majority of the minerals are found below a plant community known as Savana Metalo fila, or ªCangaº, which represents only 3% of the landscape within the CarajaÂs National Forest (CNF). The aim of our study was to understand the diversity of community of non-volant small mammals in the two predominant vegetation types: Ombrophilous Forest and Canga, and to examine how mining impacts these communities. Sampling was conducted from January 2010 to August 2011 in 11 sampling sites divided by the total area of Canga …

Nucleoside-Diphosphate-Kinase Of P. Gingivalis Is Secreted From Epithelial Cells In The Absence Of A Leader Sequence Through A Pannexin-1 Interactome, Kalina Atanasova, Jungnam Lee, Joann Roberts, Kyulim Lee, David M. Ojcius, Özlem Yilmaz

All Dugoni School of Dentistry Faculty Articles

Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to …

Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel

USF Tampa Graduate Theses and Dissertations

Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether …

The Effects Of Phytohormones And Isoprenoids In Dihydroartemisinin-Induced Dormancy In The Erythrocytic Stages Of Plasmodium Falciparum, Marvin Duvalsaint Duvalsaint

USF Tampa Graduate Theses and Dissertations

Our ability to control malaria has been challenged by increasing antimalarial resistance. Plasmodium falciparum undergoes dormancy in the blood stages which is hypothesized to be a means by which they are able to survive under drug pressure. This helps select for resistant parasites which grow following removal of drug. The mechanisms behind dormancy and the subsequent recrudescence are not fully understood but translating knowledge from related organisms which undergo a similar phenomenon might shed some light. Higher plants utilize dormancy during the early development stages to survive under unfavorable conditions, increasing fitness of the seedling and ensuring viability when this …

Current Antibiotics And Future Herbal Extract Methods To Treat Methicillin-Resistant Staphylococcus Aureus (Mrsa): Focusing On Inhibition Of Penicillin-Binding Protein 2a (Pbp2a), Mgayya R. Makullah

Senior Honors Theses

Methicillin-Resistant Staphylococcus aureus (MRSA) has developed resistance towards a number of antibiotics. This resistance creates a challenge when trying to treat MRSA with a number of antibiotics. This is mainly caused by the penicillin-binding proteins 2a (PBP2a). PBP2a have significantly less affinity for beta-lactam antibiotics compared to the other penicillin-binding proteins (PBPs) expressed by non-resistant strains. New treatments involving a combination of antibiotics and herbal extracts are being developed and used to inactivate PBP2a, allowing the previous ineffective antibiotics to be more effective.

An Iron Detection System Determines Bacterial Swarming Initiation And Biofilm Formation, Chuan-Sheng Lin, Yu-Huan Tsai, Chih-Jung Chang, Shun-Fu Tseng, Tseng-Ru Wu, Chia-Chen Lu, Ting-Shu Wu, Jang-Jih Lu, Jim-Tong Horng, Jan Martel, David M. Ojcius, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe³⁺) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. …

Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino

Pediatrics Faculty Publications

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that ( …

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown …

The Life Cycle Stages Of Pneumocystis Murina Have Opposing Effects On The Immune Response To This Opportunistic Fungal Pathogen, Heather M. Evans, Grady L. Bryant Iii, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina. The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and …

Pyk2 Activates The Nlrp3 Inflammasome By Directly Phosphorylating Asc And Contributes To Inflammasome-Dependent Peritonitis, I-Che Chung, Chun-Nan Ouyang, Sheng-Ning Yuan, Hsin-Pai P. Li, Jeng-Ting Chen, Hui-Ru Shieh, Yu-Jen Chen, David M. Ojcius, Ching-Liang Chu, Jau-Song Yu, Yu-Sun Chang, Lih-Chyang Chen

All Dugoni School of Dentistry Faculty Articles

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, …

Building Viral Replication Organelles: Close Encounters Of The Membrane Types, Peter D. Nagy, Jeroen R. P. M. Strating, Frank J. M. Van Kuppeveld

Plant Pathology Faculty Publications

Positive-strand (+)RNA viruses are important and emerging pathogens of humans, animals, and plants. Upon infection, they induce the formation of specialized membranous replication organelles with unique lipid composition to facilitate robust virus replication. In this article, the authors discuss the proviral role of virus-induced membrane contact sites (vMCSs). The emerging picture is that vMCSs channel lipids to viral membranes and tune the lipid composition for optimal generation and functioning of replication organelles.

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

Modeling Cross-Species Extrapolation Of Inhalation Anthrax For Risk Assessment Purposes, Megan O. Powell

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Vaccination Strategies For Small Worlds, Winfried Just, Hannah L. Callender

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Sphingosine 1-Phosphate Activation Of Egfr As A Novel Target For Meningitic Escherichia Coli Penetration Of The Blood-Brain Barrier, Xiangru Wang, Ravi Maruvada, Andrew J. Morris, Jun O. Liu, Michael J. Wolfgang, Dong Jae Baek, Robert Bittman, Kwang Sik Kim

Internal Medicine Faculty Publications

Central nervous system (CNS) infection continues to be an important cause of mortality and morbidity, necessitating new approaches for investigating its pathogenesis, prevention and therapy. Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, which develops following penetration of the blood–brain barrier (BBB). By chemical library screening, we identified epidermal growth factor receptor (EGFR) as a contributor to E. coli invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS-infecting E. coli exploited sphingosine 1-phosphate (S1P) for EGFR activation in penetration of the BBB in vitro and in vivo. We …

Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H. Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I. Bukrinsky, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the …