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Articles 1 - 20 of 20
Full-Text Articles in Medicine and Health Sciences
Cyclic Di-Gmp Regulates Motility, Biofilm Formation, And Desiccation Tolerance In Acinetobacter Baumannii, Garrett Reynolds
Cyclic Di-Gmp Regulates Motility, Biofilm Formation, And Desiccation Tolerance In Acinetobacter Baumannii, Garrett Reynolds
Electronic Theses and Dissertations
Acinetobacter baumannii is an increasingly multidrug-resistant pathogen contributing to hospital-acquired infections necessitating the discovery of novel treatments. A bacterial second messenger, cyclic diguanosine monophosphate (cyclic di-GMP), can regulate various persistence factors that are potentially advantageous for survival in hospital environments. Cyclic di-GMP–modulating enzymes and cyclic di-GMP–binding effectors predictively are encoded in the Acinetobacter baumannii genome. I hypothesized that cyclic di-GMP controls motility, biofilm formation, and desiccation tolerance in Acinetobacter baumannii. Disrupting cyclic di-GMP–modulating enzymes or cyclic di-GMP–binding effectors should alter the regulatory effectiveness of these phenotypes. I tested the multidrug-resistant isolate Acinetobacter baumannii strain AB5075 and identified several transposon …
Decoding The Mystery Of Antibiotic Persistence, Tahmina Hossain
Decoding The Mystery Of Antibiotic Persistence, Tahmina Hossain
Electronic Theses and Dissertations
This work combines microbiology, molecular biology, Next-Generation Sequencing and system biology approaches to explore the mechanism of antibiotic persistence: a multi-drug tolerant, non-dividing, and metabolically altered state present in a subpopulation of cells due to phenotypic diversity rather than genetic variation (i.e. mutations). Persister can survive lethal antibiotic state and resuscitate after the treatment period is over. They are considered as the major contributing factor behind recurring infections. They also have a high mutation rate, which increases the chances of bacteria gaining antibiotic resistance. The formation of this phenotypic variant (persister) threatens the therapeutic effectiveness of antibiotics and understanding how …
Genital Chlamydia Infection Is Influenced By The Female Sex Hormones Estrogen And Progesterone In Vivo, Amy Gail Gravitte
Genital Chlamydia Infection Is Influenced By The Female Sex Hormones Estrogen And Progesterone In Vivo, Amy Gail Gravitte
Electronic Theses and Dissertations
Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. It often goes unnoticed due to lack of symptoms and left untreated it can ascend the female genital tract to cause sequelae like pelvic inflammatory disease and irreversible tubal infertility. In reproductive-aged women, female sex hormones estrogen (E2) and progesterone (P4) concentrations fluctuate during the menstrual cycle and are influenced by hormonal contraceptives and hormone replacement therapy. E2 and P4 influence genital Chlamydia infection in women and mice, but these multifactorial interactions are not entirely mapped out. The complex interplay of E2 and P4 with …
The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe
The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe
Electronic Theses and Dissertations
Alphaviruses are mosquito-borne arboviruses that have a positive sense, single-stranded RNA genome, which are capable of causing severe disease and thus pose a significant burden to public health. During alphaviral replication, significant quantities of viral genomic RNAs that lack the canonical alphaviral 5’ cap structure are produced and packaged into viral particles, despite the fact that these noncapped genomes cannot be translated and are essentially noninfectious. The production and packaging of the noncapped genomes has been found to be true for infections across multiple vertebrate and invertebrate cell lines and alphavirus species, although the proportion of ncgRNA produced differs. Despite …
A New All-Natural Wound Treatment Gel Shows Strong Inhibitory Activity Against Staphylococcus Aureus And Other Wound Pathogens, Tasha K. Nelson
A New All-Natural Wound Treatment Gel Shows Strong Inhibitory Activity Against Staphylococcus Aureus And Other Wound Pathogens, Tasha K. Nelson
Electronic Theses and Dissertations
Skin related injuries are some of the most dangerous forms of wounds. In addition to treating the wound itself, health care providers must be cautious of microbial infections. In this study, we evaluate a novel all-natural antimicrobial gel compound (AMG) designed to kill planktonic bacteria, penetrate bacterial biofilms, and accelerate wound healing. In -vitro experiments demonstrate that AMG is effective in inhibiting planktonic growth and biofilm development of eight common pathogens. LIVE/DEAD staining and confocal microscopy reveal that planktonic growth and three-dimensional structure of biofilms were significantly reduced. Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) was used to investigate a small …
Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb
Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb
Electronic Theses and Dissertations
Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …
Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding
Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding
Electronic Theses and Dissertations
Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …
Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao
Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao
Electronic Theses and Dissertations
Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection leads to a phenomenon of inflammaging, in which chronic infection or inflammation induces an immune aged phenotype with T cell dysfunction. Thus, HCV or HIV infection has been deemed as a model to study the mechanisms of T cell infammaging and viral persistence in humans. In this dissertation, T cell homeostasis, DNA damage and repair machineries were investigated in patients with chronic HCV or HIV infection at risk for inflammaging. We found a significant depletion in CD4 T cells, which was correlated with their apoptosis in chronically HCV/HIVinfected patients, compared …
Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey
Electronic Theses and Dissertations
Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors …
Characterizing The Role Of Fungal Shape In A Zebrafish Model Of Invasive Candidiasis, Brittany Seman
Characterizing The Role Of Fungal Shape In A Zebrafish Model Of Invasive Candidiasis, Brittany Seman
Electronic Theses and Dissertations
Candida albicans is a common hospital-acquired fungal infection, and disseminated disease claims up to one-half of those afflicted. C. albicans has a unique ability to differentiate its shape during infection, and this differentiation is thought to be a major virulence factor during invasive infections. Each shape is proposed to have a specialized role: filaments drive tissue invasion and yeast mediate dissemination to the bloodstream. However, it has been difficult to test these hypotheses for two reasons. First, rigorous testing of shape-specific roles requires diverse strategies of shape modulation that restrict the possibility of manipulation-specific artifacts. Second, although connecting shape to …
Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best
Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best
Electronic Theses and Dissertations
Legionella pneumophila is an environment organism that parasitizes a wide range of protozoa. Growth within the environmental host primes L. pneumophila for infection of human alveolar macrophages when contaminated aerosols are inhaled. Intracellular replication within either host requires the establishment a replicative niche, known as the Legionella-containing vacuole (LCV). Biogenesis of the LCV depends on the type IVb translocation system, the Dot/Icm, to translocation >320 effectors into the host cytosol. Effectors are responsible for preventing lysosome fusion to the LCV, recruitment of ER-derived vesicles to the LCV, and modulation of a plethora of host processes to promote the intracellular …
Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde
Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde
Electronic Theses and Dissertations
Silicosis is an irreversible lung inflammatory disease caused by chronic exposure to crystalline silica (CS) and is one of the most prevalent occupational diseases worldwide. Lipid chemoattractant Leukotriene B4 (LTB4) plays an important role in neutrophilic inflammation that drives silicosis and promotes lung cancer. Previous studies in our laboratory have demonstrated that CS-induced neutrophilic inflammation and lung tumor burden in K-rasLA1 mice is abrogated in the LTB4-receptor deficient mice. Another pathway whose importance is well studied in the progression of silicosis is the Nalp3 inflammasome pathway. Studies have shown inflammasome- dependent IL-1b to be …
Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta
Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta
Electronic Theses and Dissertations
Neutrophils respond to bacterial LPS through Toll-like receptor 4 (TLR4), which activates or potentiates immune defensive functions and prolongs cell survival. Activation of TLR4 signaling in neutrophils is beneficial for effective clearance of LPS-bearing Gram-negative bacteria, but may also drive aberrant inflammation if not stringently regulated. The regulatory processes by which neutrophil functions are calibrated to respond appropriately to different LPS-bearing bacteria are incompletely understood. Described here are investigations that reveal an unexpected sensitivity of TLR4 in neutrophils to small changes in LPS structure typical of various Gram-negative bacteria, including those that are dangerously virulent (Escherichia coli and Salmonella …
Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke
Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke
Electronic Theses and Dissertations
Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall …
In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah
In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah
Electronic Theses and Dissertations
Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a …
Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall
Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall
Electronic Theses and Dissertations
Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …
Immunomodulation Of Myeloid-Derived Suppressor Cells By Particulate B-Glucan In Cancer., Sabrin Husein Albeituni
Immunomodulation Of Myeloid-Derived Suppressor Cells By Particulate B-Glucan In Cancer., Sabrin Husein Albeituni
Electronic Theses and Dissertations
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we investigated the effect of dectin-1 stimulation by yeast-derived particulate β-glucan in MDSC function and differentiation in cancer. In vivo treatment of mice bearing lewis lung carcinoma and mammary cell carcinoma with particulate β-glucan decreased tumor weight and splenomegaly, and reduced the accumulation of polymorphonuclear-MDSC (PMN-MDSC) but not monocytic-MDSC (M-MDSC) in the spleen and tumor. In addition, particulate β-glucan differentially modulated the function of different MDSC subsets; it enhanced PMN-MDSC respiratory burst and apoptosis, and induced the differentiation of M-MDSC into …
Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey
Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey
Electronic Theses and Dissertations
Pseudomonas aeruginosa, a Gram-negative bacillus, commonly infects immunocompromised individuals and uses a variety of virulence factors to persist in these hosts. The posttranscriptional regulator, RsmA, plays a role in the expression of many virulence factors in P. aeruginosa. RsmA up regulates virulence factors used in colonizing hosts. However, regulation of rsmA is not well elucidated. Transposon mutagenesis was performed on P. aeruginosa containing a transcriptional rsmA-lacZ fusion to answer this question. Mutants were screened via β-galactosidase assay and transposon insertions identified via arbitrary PCR. A probable MFS transporter, we named mtpX, was one significant transposon mutant identified. …
The Involvement Of Beta-Catenin In The Inflammatory Response Leading To Autoimmune Diabetes Development., Arin Lee Zirnheld
The Involvement Of Beta-Catenin In The Inflammatory Response Leading To Autoimmune Diabetes Development., Arin Lee Zirnheld
Electronic Theses and Dissertations
We identified and characterized a novel defect in β-catenin expression in bone marrow derived dendritic cells (BMDC) from NOD mice, a model for human Type I diabetes. This protein is expressed at high levels throughout the lifespan of the mouse and correlates with increased pro-inflammatory cytokine production by the BMDC and IFNγ induction by T cells cocultured with the BMDC. These defects, including a similar pattern of pro-inflammatory cytokine production, are also observed in human monocytederived DC from diabetic patients. After exploring several potential mechanisms involved in the accumulation of β-catenin in NOD BMDC, we found that β-catenin is phosphorylated …
Characterization Of Seca-Sod Operon In Borrellia Burgdorferi., Tonya Lynn Nichols
Characterization Of Seca-Sod Operon In Borrellia Burgdorferi., Tonya Lynn Nichols
Electronic Theses and Dissertations
Borrelia burgdorferi, the causative agent of Lyme disease, has been characterized as a microaerophilic spirochete. O2 consumption and utilization potentially yield reactive oxygen intermediates, such as superoxide, hydroxyl radicals, and hydrogen peroxide. This study investigated the expression of the sod gene, which encodes the only, identified oxidative defense mechanism in B. burgdorferi. Using primer extension analysis and RT-PCR, it was found that sod and secA are organized as a single transcriptional unit under the control of σ70-like promoter upstream of the secA open reading frame. Generally, gene expression decreases with increased distance from the promoter; however, secA expression was observed …