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Articles 1 - 21 of 21
Full-Text Articles in Microbiology
Enterobactin-Based Immune Interventions Against Gram-Negative Bacterial Infections, Huiwen Wang
Enterobactin-Based Immune Interventions Against Gram-Negative Bacterial Infections, Huiwen Wang
Doctoral Dissertations
Enterobactin (Ent)-mediated iron acquisition is critical for many Gram-negative bacteria to survive in the host. Given the bacteriostatic effect of lipocalin-2 resulting from its potent Ent-binding ability, immune interventions directly targeting Ent is a promising antimicrobial strategy against Gram-negative bacterial infections. Moreover, hyperimmune egg yolk antibody is an emerging passive immune agent for the control of bacterial infections. Oral administration of anti-Ent egg yolk antibody may confer passive immune protection against Ent-dependent enteric pathogens. In this dissertation study, multidisciplinary approaches in conjunction with different model systems (in vitro, in vivo, and ex vivo) were used to …
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 …
Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones
Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones
Doctoral Dissertations
Systems biology offers the opportunity to understand the complex mechanisms of various biological phenomena. The wealth of data that is produced, at an increasing rate, provides the potential to meet this opportunity. Here we take an applied approach to integrate multiple omic level data sources in order to generate biologically relevant hypotheses. We apply a novel analysis pipeline to model both, in concert, the microbial and transcriptomic signature from COVID-19 positive patients. We show patients may suffer from an increased microbial burden, with an increased pathogen potential. Gene expression evidence further shows patients may exhibit a compromised barrier immunity, owing …
Oncolytic Viruses: Cancer Treatment Going Viral, Rhianna N. Bronson
Oncolytic Viruses: Cancer Treatment Going Viral, Rhianna N. Bronson
Chancellor’s Honors Program Projects
No abstract provided.
Improving Aedes Mosquito Surveillance And La Crosse Virus Screening In Eastern Tennessee, Cassandra Urquhart
Improving Aedes Mosquito Surveillance And La Crosse Virus Screening In Eastern Tennessee, Cassandra Urquhart
Masters Theses
La Crosse virus (LACV), transmitted by infected Aedes triseriatus, Ae. albopictus, and Ae. japonicus mosquitoes is the leading cause of pediatric arboviral encephalitis. Severe cases of LAC encephalitis occur in individuals 16-years-old or younger and may cause permanent neurological damage or fatality. No vaccines exist making mosquito control and disease prevention crucial to public health. Effective screening and surveillance practices are key components to these goals. While a number of standard mosquito surveillance methods exist, continuous testing and improved understanding of vector biology to determine the best ways to implement these methods is important. Additionally, the current standard …
Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford
Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford
Pursuit - The Journal of Undergraduate Research at The University of Tennessee
Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …
Role Of Surface Antigens Of Mycobacterium Spp. In Diagnosis, Ashutosh Wadhwa
Role Of Surface Antigens Of Mycobacterium Spp. In Diagnosis, Ashutosh Wadhwa
Doctoral Dissertations
Mycobacterial species are ubiquitous in nature and a worldwide concern for human and animal health. The major mycobacterial infections in animals are Johne’s disease (JD) and bovine tuberculosis (bTB). Controlling these infections is difficult due to the lack of highly sensitive and sensitive diagnostic test. Currently available diagnostic tests have to be carried out in laboratory settings with well experienced and trained examiners. My goal is to develop a sensitive on-site (in-field) device for diagnosis of Johne’s disease and bovine tuberculosis. The specific aims of this thesis were (1) to review currently-used or recently developed diagnostic tests for mycobacterial infections, …
Development And Application Of Liquid Chromatography-Tandem Mass Spectrometry Methods To The Understanding Of Metabolism And Cell-Cell Signaling In Several Biological Systems, Jessica Renee Gooding
Development And Application Of Liquid Chromatography-Tandem Mass Spectrometry Methods To The Understanding Of Metabolism And Cell-Cell Signaling In Several Biological Systems, Jessica Renee Gooding
Doctoral Dissertations
Liquid chromatography tandem mass spectrometry has become a powerful tool for investigating biological systems. Herein we describe the development of both isotope dilution mass spectrometry methods and targeted metabolomics methods for the study of metabolic and cell-cell signaling applications.
A putative yeast enzyme was characterized by discovery metabolite profiling, kinetic flux profiling, transcriptomics and structural biology. These experiments demonstrated that the enzyme shb17 was a sedoheptulose bisphosphatase that provides a thermodynamically dedicated step towards riboneogenesis, leading to the redefinition of the canonical pentose phosphate pathway.
An extension of metabolic profiling and kinetic flux profiling methods was developed for a set …
Functional Cloning And Characterization Of Antibiotic Resistance Genes From The Chicken Gut Microflora, Wei Zhou
Masters Theses
A recent study using human fecal samples in conjunction with a culture-independent approach revealed immense diversity of antibiotic resistance (AR) genes in the human gut microflora. We hypothesize that food animal gut microflora also contain diverse and novel AR genes which could contribute to the emergence and transmission of AR in pathogens important in animal and human health. To test this, we examined AR reservoir in chicken gut microflora using a metagenomic, functional cloning method. Total genomic DNA was extracted from individual cecal contents of two free range chickens and two conventionally raised chickens. The DNAs were physically sheered into …
Naïve T Cells Re-Distribute To The Lungs Of Selectin Ligand Deficient Mice, Thandi M. Onami, John R. Harp
Naïve T Cells Re-Distribute To The Lungs Of Selectin Ligand Deficient Mice, Thandi M. Onami, John R. Harp
Microbiology Publications and Other Works
BACKGROUND: Selectin mediated tethering represents one of the earliest steps in T cell extravasation into lymph nodes via high endothelial venules and is dependent on the biosynthesis of sialyl Lewis X (sLe(x)) ligands by several glycosyltransferases, including two fucosyltransferases, fucosyltransferase-IV and -VII. Selectin mediated binding also plays a key role in T cell entry to inflamed organs.
METHODOLOGY/PRINCIPAL FINDINGS: To understand how loss of selectin ligands (sLe(x)) influences T cell migration to the lung, we examined fucosyltransferase-IV and -VII double knockout (FtDKO) mice. We discovered that FtDKO mice showed significant increases (approximately 5-fold) in numbers of naïve T cells in …
The Generation Of Influenza-Specific Humoral Responses Is Impaired In St6gal I-Deficient Mice., Thandi M. Onami, J Zeng, H. M. Joo, B. Rajini, J. P. Wrammert, M. Y. Sangster
The Generation Of Influenza-Specific Humoral Responses Is Impaired In St6gal I-Deficient Mice., Thandi M. Onami, J Zeng, H. M. Joo, B. Rajini, J. P. Wrammert, M. Y. Sangster
Microbiology Publications and Other Works
Posttranslational modification of proteins, such as glycosylation, can impact cell signaling and function. ST6Gal I, a glycosyltransferase expressed by B cells, catalyzes the addition of alpha-2,6 sialic acid to galactose, a modification found on N-linked glycoproteins such as CD22, a negative regulator of B cell activation. We show that SNA lectin, which binds alpha-2,6 sialic acid linked to galactose, shows high binding on plasma blasts and germinal center B cells following viral infection, suggesting ST6Gal I expression remains high on activated B cells in vivo. To understand the relevance of this modification on the antiviral B cell immune response, we …
Role Of Chromodomain Helicase Dna-Binding Protein 2 In Dna Damage Response Signaling And Tumorigenesis., Thandi M. Onami, P. Nagarajan, S. Rajagopalan, S. Kania, R. Donnell, S. Venkatachalam
Role Of Chromodomain Helicase Dna-Binding Protein 2 In Dna Damage Response Signaling And Tumorigenesis., Thandi M. Onami, P. Nagarajan, S. Rajagopalan, S. Kania, R. Donnell, S. Venkatachalam
Microbiology Publications and Other Works
The chromodomain helicase DNA-binding proteins (CHDs) are known to affect transcription through their ability to remodel chromatin and modulate histone deacetylation. In an effort to understand the functional role of the CHD2 in mammals, we have generated a Chd2 mutant mouse model. Remarkably, the Chd2 protein appears to play a critical role in the development, hematopoiesis and tumor suppression. The Chd2 heterozygous mutant mice exhibit increased extramedullary hematopoiesis and susceptibility to lymphomas. At the cellular level, Chd2 mutants are defective in hematopoietic stem cell differentiation, accumulate higher levels of the chromatin-associated DNA damage response mediator, cH2AX, and exhibit an aberrant …
Systemic And Mucosal Infection Program Protective Memory Cd8 T Cells In The Vaginal Mucosa., Thandi M. Onami, P. K. Suvas, H. M. Dech, J. Zeng
Systemic And Mucosal Infection Program Protective Memory Cd8 T Cells In The Vaginal Mucosa., Thandi M. Onami, P. K. Suvas, H. M. Dech, J. Zeng
Microbiology Publications and Other Works
Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of Ag-specific CD8 T cells in tissues, including the vaginal mucosa. Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2-3x more Ag-specific CD8 T cells that coexpress both IFN-gamma and TNF-alpha in comparison to the intranasal route of …
Lack Of Antigen-Specific Tissue Remodeling In Mice Deficient In The Macrophage Galactose-Type Calcium-Type Lectin 1/Cd301a., Thandi M. Onami, K. Sato, Y. Imai, N. Higashi, Y. Kumamoto, S. M. Hedrick, T. Irimura
Lack Of Antigen-Specific Tissue Remodeling In Mice Deficient In The Macrophage Galactose-Type Calcium-Type Lectin 1/Cd301a., Thandi M. Onami, K. Sato, Y. Imai, N. Higashi, Y. Kumamoto, S. M. Hedrick, T. Irimura
Microbiology Publications and Other Works
Macrophage galactose-type C-type lectins (MGLs), which were recently named CD301, have 2 homologues in mice: MGL1 and MGL2. MGLs are expressed on macrophages and immature dendritic cells. The persistent presence of granulation tissue induced by a protein antigen was observed in wild-type mice but not in mice lacking an endogenous, macrophage-specific, galactose-type calcium-type lectin 1 (MGL1) in an air pouch model. The anti-MGL1 antibody suppressed the granulation tissue formation in wild-type mice. A large number of cells, present only in the pouch of MGL1-deficient mice, were not myeloid or lymphoid lineage cells and the number significantly declined after administration of …
Cd43 Modulates Severity And Onset Of Experimental Autoimmune Encephalomyelitis., Thandi M. Onami, M. L. Ford, A. Sperling, R. Ahmed, B. D. Evavold
Cd43 Modulates Severity And Onset Of Experimental Autoimmune Encephalomyelitis., Thandi M. Onami, M. L. Ford, A. Sperling, R. Ahmed, B. D. Evavold
Microbiology Publications and Other Works
Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis characterized by infiltration of activated CD4(+) T lymphocytes into tissues of the CNS. This study investigated the role of CD43 in the induction and progression of EAE. Results demonstrate that CD43-deficient mice have reduced and delayed clinical and histological disease severity relative to CD43(+/+) mice. This reduction was characterized by decreased CD4(+) T cell infiltration of the CNS of CD43(-/-) mice but similar numbers of Ag-specific T cells in the periphery, suggesting a defect in T cell trafficking to the CNS. The absence of CD43 also affected cytokine production, …
Primary And Secondary Immunocompetence In Mixed Allogeneic Chimeras, Thandi M. Onami, M. A. Williams, A. B. Adams, M. B. Walsh, N. Shirasugi, T. C. Pearson, R. Ahmed, C. P. Larsen
Primary And Secondary Immunocompetence In Mixed Allogeneic Chimeras, Thandi M. Onami, M. A. Williams, A. B. Adams, M. B. Walsh, N. Shirasugi, T. C. Pearson, R. Ahmed, C. P. Larsen
Microbiology Publications and Other Works
Targeted disruption of T cell costimulatory pathways, particularly CD28 and CD40, has allowed for the development of minimally myeloablative strategies for the induction of mixed allogeneic chimerism and donor-specific tolerance across full MHC barriers. In this study we analyze in depth the ability of mixed allogeneic chimeras in two strain combinations to mount effective host-restricted and donor-restricted antiviral CD4 and CD8 responses, as well as the impact of development of mixed chimerism on the maintenance of pre-existing memory populations. While antiviral CD8 responses in mixed chimeras following acute viral infection with lymphocytic choriomeningitis virus Armstrong or vaccinia virus are largely …
Tcr Signal Transduction In Antigen-Specific Memory Cd8 T Cells, Thandi M. Onami, Ellen N. Kersh, Susan M. Kaech, Miriana Moran, E. John Wherry, M. Carrie Miceli, Rafi Ahmed
Tcr Signal Transduction In Antigen-Specific Memory Cd8 T Cells, Thandi M. Onami, Ellen N. Kersh, Susan M. Kaech, Miriana Moran, E. John Wherry, M. Carrie Miceli, Rafi Ahmed
Microbiology Publications and Other Works
Memory T cells are more responsive to Ag than naive cells. To determine whether memory T cells also have more efficient TCR signaling, we compared naive, effector, and memory CD8 T cells of the same antigenic specificity. Surprisingly, initial CD3 signaling events are indistinguishable. However, memory T cells have more extensive lipid rafts with higher phosphoprotein content before TCR engagement. Upon activation in vivo, they more efficiently induce phosphorylation of-LAT (linker for activation of T cells), ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38. Thus, memory CD8 T cells do not increase their TCR sensitivity, but are better …
Cutting Edge: Persistent Viral Infection Prevents Tolerance Induction And Escapes Immune Control Following Cd28/Cd40 Blockade-Based Regimen, Thandi M. Onami, M. A. Williams, A. B. Adams, M. M. Durham, T. C. Pearson, R. Ahmed, C. P. Larsen
Cutting Edge: Persistent Viral Infection Prevents Tolerance Induction And Escapes Immune Control Following Cd28/Cd40 Blockade-Based Regimen, Thandi M. Onami, M. A. Williams, A. B. Adams, M. M. Durham, T. C. Pearson, R. Ahmed, C. P. Larsen
Microbiology Publications and Other Works
A continuing concern with CD28 and/or CD40 blockade-based strategies to induce tolerance and mixed chimerism is their potential to disrupt protective immunity to preexisting infections. In this report, we find that preexisting persistent infection with lymphocytic choriomeningitis virus (LCMV) clone 13 prevents the induction of tolerance, mixed chimerism, and donor-reactive T cell deletion. Mice continue to be refractory to tolerance induction even after viremia has been resolved and virus is present only at very low levels in peripheral tissues. Conversely, we find that the full tolerance regimen, or costimulation blockade alone, specifically inhibits already ongoing antiviral immune responses, leading to …
Molecular Cloning And Characterization Of A Novel Mouse Macrophage C-Type Lectin, Mmgl2, Which Has A Distinct Carbohydrate Specificity From Mmgl1, Thandi M. Onami, M. Tsuiji, M. Fujimori, Y. Ohashi, N. Higashi, S. M. Hendrick, T. Irimura
Molecular Cloning And Characterization Of A Novel Mouse Macrophage C-Type Lectin, Mmgl2, Which Has A Distinct Carbohydrate Specificity From Mmgl1, Thandi M. Onami, M. Tsuiji, M. Fujimori, Y. Ohashi, N. Higashi, S. M. Hendrick, T. Irimura
Microbiology Publications and Other Works
A novel mouse macrophage galactose-type C-type lectin 2 (mMGL2) was identified by BLAST analysis of expressed sequence tags. The sequence of mMGL2 is highly homologous to the mMGL, which should now be called mMGL1. The open reading frame of mMGL2 contains a sequence corresponding to a type II transmembrane protein with 332 amino acids having a single extracellular C-type lectin domain. The 3'-untranslated region included long terminal repeats of mouse early transposon. The Mgl2 gene was cloned from a 129/SvJ mouse genomic library and sequenced. The gene spans 7,136 base pairs and consists of 10 exons, which is similar to …
Generation Of Mice Deficient For Macrophage Galactose- And N-Acetylgalactosamine-Specific Lectin: Limited Role In Lymphoid And Erythroid Homeostasis And Evidence For Multiple Lectins, Thandi M. Onami, M. Y. Lin, D. M. Page, S. A. Reynolds, C. D. Katayama, J. D. Marth, T. Irimura, A. Varki, N. Varki, S. M. Hedrick
Generation Of Mice Deficient For Macrophage Galactose- And N-Acetylgalactosamine-Specific Lectin: Limited Role In Lymphoid And Erythroid Homeostasis And Evidence For Multiple Lectins, Thandi M. Onami, M. Y. Lin, D. M. Page, S. A. Reynolds, C. D. Katayama, J. D. Marth, T. Irimura, A. Varki, N. Varki, S. M. Hedrick
Microbiology Publications and Other Works
Macrophage receptors function in pattern recognition for the induction of innate immunity, in cellular communication to mediate the regulation of adaptive immune responses, and in the clearance of some glycosylated cells or glycoproteins from the circulation. They also function in homeostasis by initiating the engulfment of apoptotic cells. Evidence has suggested that macrophage receptors function to recognize cells that are destined for programmed cell death but not yet overtly apoptotic. We have examined the function of a macrophage receptor specific for unsialylated glycoproteins, known as the mouse macrophage galactose- and N-acetylgalactosamine-specific lectin (mMGL) (Ii et al., J. Biol. Chem. 265:11295-11298, …
Dynamic Regulation Of T Cell Immunity By Cd43, Thandi M. Onami, L. E. Harrington, M. A. Williams, M. Galvan, C. P. Larsen, T. C. Pearson, N. Manjunath, L. G. Baum, B. D. Pearce, R. Ahmed
Dynamic Regulation Of T Cell Immunity By Cd43, Thandi M. Onami, L. E. Harrington, M. A. Williams, M. Galvan, C. P. Larsen, T. C. Pearson, N. Manjunath, L. G. Baum, B. D. Pearce, R. Ahmed
Microbiology Publications and Other Works
During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis of CD43(-/-) mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific CD8 T cells from -/- mice compared with +/+ mice. Furthermore, we examined the role of CD43 in the kinetics of an immune response. We show that CD43 expression modestly effects generation of a primary virus-specific …