Microbiology Commons^™

The Role Of Dendritic Cell Subsets And Innate Immunity In The Pathogenesis Of Type 1 Diabetes And Other Autoimmune Diseases, Jeffrey D. Price, Kristin V. Tarbell

Nebraska Center for Virology: Faculty Publications

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in …

Application Of Supervised Machine Learning Algorithms For Rapid Identification Of Mrsa Pfge Strain Types, Michael L. Bernauer

Biomedical Informatics Seminar Series (BioMISS)

Introduction: Pulsed-field gel electrophoresis (PFGE) is a molecular typing method used in epidemiologic surveillance of MRSA. PFGE relies on electrophoretic migration of restricted DNA fragments, resulting in characteristic fingerprints which can be used to classify organisms. Current methods of analysis, such as Gel Compar II and BioNumerics rely on unsupervised hierarchical clustering algorithms to group organisms based on pairwise similarity. These methods are labor intensive, often requiring a significant amount of user intervention and oversight. This study presents an automated approach to PFGE typing to reduce the amount of user involvement and time required for analysis.

Methods: A total of …

Adar1 Facilitates Hiv-1 Replication In Primary Cd4+ T Cells., Eloy Cuadrado, Thijs Booiman, John L Van Hamme, Machiel H Jansen, Karel A Van Dort, Adeline Vanderver, Gillian I Rice, Yanick J Crow, Neeltje A Kootstra, Taco W Kuijpers

Neurology Faculty Publications

Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of …

Herpes Virus Infections, Inflammatory Markers And Risk Of Developing T2dm And Cvd: An Analysis Of Nhanes With Adults, Aged 20-49, 1999-2010, Margarita Irizarry-De La Cruz

Walden Dissertations and Doctoral Studies

Herpes simplex viruses (HSVs), are among the most virulent and widespread pathogens; they affect 60-90% of the population worldwide. Substantial evidence indicates a possible association between pathogens and chronic disease. HSVs, among other viruses, have been associated with increased risk for inflammatory diseases. However, prior findings have been inconsistent on the role of infection in triggering autoimmune response and chronic disease. This study builds on the premise that pathogens can induce an inflammatory response and increase the risk for disease development. A representative U.S. sample from NHANES, a national population-based cross-sectional survey, was used to examine the relationship between HSVs …

Signaling Between Two Sensor Kinases Controls Biofilms And Host Colonization In A Bacterial Symbiont, Allison N. Norsworthy

Dissertations

Organisms within all domains of life must acclimate to fluctuating environments to survive. To do this, cells utilize sensory circuits, which function to connect environmental stimuli to an intracellular response. One common sensory pathway utilized by bacteria is two-component signaling (TCS), composed of an environmental sensor (the sensor kinase, SK) and a cognate, intracellular effector (the response regulator, RR). The marine bacterium Vibrio fischeri uses an elaborate TCS phosphorelay containing a hybrid SK, RscS, and two RRs, SypE and SypG, to colonize its natural squid host, Euprymna scolopes. This TCS pathway regulates V. fischeri's ability to form a biofilm, or …

The Effect Of Antibiotics On Pseudomonas Aeruginosa Biofilm Production, Courtney Paige Turpin

Online Theses and Dissertations

Antibiotic-resistant bacteria have become an increasing burden worldwide. A highly resistant species is Pseudomonas aeruginosa, a nosocomial pathogen that produces a biofilm that enhances its resistance. This project examined the possibility of using bacteriocin, an internal protective toxin produced by some species of bacteria, as a potential treatment for resistant bacteria. In this study, standard broad spectrum antibiotics were used to treat P. aeruginosa to prevent biofilm formation. The biofilm was then analyzed to determine if the biofilm is inhibited or facilitated by each treatment. Optimal concentrations of antibiotics were determined to be effective at a concentration of 0.07mg/mL for …

Antimicrobial Efficacy Of Natural Bioactive Compounds And High Pressure Processing Against Potential Pathogens In Infant Foods, Hayriye Cetin-Karaca

Theses and Dissertations--Animal and Food Sciences

This study investigated the antimicrobial efficacy of bioactive plant compounds along with high pressure processing (HPP) against pathogens Bacillus cereus and Cronobacter sakazakii in infant formula and infant rice cereal. The influence of these applications on antimicrobial activity, shelf-life and sensory attributes of infant foods were examined.

Trans-cinnamaldehyde (TC), (-)-Epigallocatechin gallate (EGCG) and [10]-Gingerol (GI) were incorporated (0.05%) in infant rice cereal reconstituted with infant formula. The cereal was inoculated with either B. cereus (ATCC 14579) or B. cereus spores (10⁷-10⁸ log CFU g^-1). All the samples were stored at 7, 23 or 37°C for …

A Nuclear Fraction Of Turnip Crinkle Virus Capsid Protein Is Important For Elicitation Of The Host Resistance Response, Sung-Hwan Kang, Feng Qu, Thomas J. Morris

Nebraska Center for Virology: Faculty Publications

The N-terminal 25 amino acids (AAs) of turnip crinkle virus (TCV) capsid protein (CP) are recognized by the resistance protein HRT to trigger a hypersensitive response (HR) and systemic resistance to TCV infection. This same region of TCV CP also contains a motif that interacts with the transcription factor TIP, as well as a nuclear localization signal (NLS). However, it is not yet known whether nuclear localization of TCV CP is needed for the induction of HRT-mediated HR and resistance. Here we present new evidence suggesting a tight correlation between nuclear inclusions formed by CP and the manifestation of HR. …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Genebased Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Inhibition Of Shp2 Suppresses Mutant Egfr-Induced Lung Tumors In Transgenic Mouse Model Of Lung Adenocarcinoma, Valentina E. Schneeberger, Yuan Ren, Noreen Luetteke, Qingling Huang, Liwei Chen, Harshani R. Lawrence, Nicholas J. Lawrence, Eric B. Haura, John M. Koomen, Domenico Coppola, Jie Wu

Molecular Biosciences Faculty Publications

Epidermal growth factor receptor (EGFR) mutants drive lung tumorigenesis and are targeted for therapy. However, resistance to EGFR inhibitors has been observed, in which the mutant EGFR remains active. Thus, it is important to uncover mediators of EGFR mutant-driven lung tumors to develop new treatment strategies. The protein tyrosine phosphatase (PTP) Shp2 mediates EGF signaling. Nevertheless, it is unclear if Shp2 is activated by oncogenic EGFR mutants in lung carcinoma or if inhibiting the Shp2 PTP activity can suppress EGFR mutant-induced lung adenocarcinoma. Here, we generated transgenic mice containing a doxycycline (Dox)-inducible PTP-defective Shp2 mutant (tetO-Shp2CSDA). Using the rat Clara …

The Νsaα Specific Lipoprotein Like Cluster (Lpl) Of S. Aureus Usa300 Contributes To Immune Stimulation And Invasion In Human Cells, Minh Thu Nguyen, Beatrice Kraft, Wenqi Yu, Dogan Doruk Demicrioglu, Tobias Hertlein, Marc Burian, Mathias Schmaler, Klaus Boller, Isabelle Bekeredjian-Ding, Knut Ohlsen, Birgit Schittek, Friedrich Götz

Molecular Biosciences Faculty Publications

All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted …

Candida Albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration, Jessica C. Hargarten, Tyler C. Moore, Thomas M. Petro, Kenneth W. Nickerson, Audrey L. Atkin

Kenneth Nickerson Papers

The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they are able to survive within and eventually escape from. C. albicans opaque cells do not secrete this chemoattractive stimulant( s). We report here a physiological mechanism that contributes to the differences in the interaction of C. …

Regulation Of Vldl Trafficking By Orp 10, Philip A. Wessels

HIM 1990-2015

Of the challenges facing the improvement of human health, none has taken the forefront quite like the endeavor to discover novel treatments for heart disease. As heart disease has now become the leading cause of death throughout the world [1], the medical community has made incredible strides in the mission to treat atherosclerosis which is the major contributor to heart disease. Very Low Density Lipoproteins (VLDL) are secreted by the liver and subsequently converted to Low Density Lipoproteins (LDL). Many factors contribute to the narrowing of the arterial walls, however oxidized LDL is the main factor that leads to the …

Application Of Fluorescence In Situ Hybridization For Visualization And Quantification Of Human Gastrointestinal Microbiota, Alexander M. Gordon

Browse all Theses and Dissertations

The microbiota of the human gastrointestinal tract is the focus of current research due to their role in human health and disease. Modern methods characterize the communities of gut microbiota through the use of culture independent techniques. Technologies such as microarrays and next generation sequencing (NGS) determine microbial profiles by analyzing the pool of 16S ribosomal small subunit RNA genes in the community. These techniques operate through the measurement of genomic content rather than through direct analysis of cells. This approach predisposes the methods to discrepancies and bias. In contrast, the use of fluorescence in situ hybridization (FISH) to analyze …

Identification Of The Molecular Mechanisms Governing The Osmotolerance Of The Emerging Gastrointestinal Pathogen Cronobacter Sakazakii, Audrey Feeney

Theses

Cronobacter sakazakii is an organism which has been associated with severe life- threatening diseases in infants and neonates. Mortality rates of up to 80% have been recorded in infants infected with Cronobacter sakazakii. Infants often suffer from septicaemia, necrotising enterocolitis and meningitis as a result of infection. A characteristic feature of the opportunistic foodborne pathogen Cronobacter sakazakii is its ability to survive in extremely arid environments such as powdered infant formula, making it a dangerous opportunistic pathogen of neonates. Herein, we provide a brief overview of the pathogen; clinical manifestations, environmental reservoirs and our current understanding of stress response mechanisms …

Exploiting Bacteriophages And Associated Peptidoglycan Hydrolases With Potential For Biocontrol In Food Related Applications, Lorraine Endersen

Theses

The work presented in this thesis describes the isolation and characterisation of novel bacteriophages, and the subsequent exploitation of their bactericidal properties against two opportunistic food related pathogens, Mycobacterium avium subsp. paratuberculosis (MAP) and Cronobacter sakazakii.

MAP is a proven animal pathogen known to cause Johne’s disease in cattle but has been implicated as a causative agent of Crohn’s disease in humans. Despite the fact that this association has yet to be proven, significant focus has been directed towards evaluating the consequences of consuming milk contaminated with MAP. Accordingly, six mycobacteriophages were isolated and characterised in terms of temperature and …

Characterisation And Applications Of Natural Lactic Acid Bacteria With Emphasis On Weissella Cibaria And Associated Exopolysaccharide, Kieran M. Lynch

Theses

The work presented in this thesis characterises natural cereal-derived lactic acid bacteria and examines their potential application in the dairy fermentation area, with special emphasis on the sourdough isolate, Weissella cibaria MGl and its associated glucan homoexopolysaccharide. This strain is notable for its high-level production of dextran, being termed a “hyper-producef’. Genome sequencing and analysis of a number of IV. cibaria strains was performed in the context of available genomic data for other Weissella species, with special focus on the metabolic traits of W. cibaria MGl, and the results represent the first study to explore members of the Weissella genus …

Increasing The Nutritional Value Of Canola Meal Via Fungal Bioprocessing, Jason R. Croat

Electronic Theses and Dissertations

The main limitation of meals from canola and other Brassica spp. is the presence of glucosinolates (GLS), which are anti-nutritional and can even be toxic at high ingestion levels. Furthermore, large amounts of GLS can reduce palatability for livestock and thus reduce intake and growth rates. For this reason canola was bred to contain lower levels of GLS (<30 >μmol/g) and erucic acid (< 2%). However, feed inclusion rates are still limited to ~30%, and this reduces the value of canola meal. The goal of this thesis was to optimize a pretreatment and fungal conversion process to enhance the nutritional value of canola meal. Various combinations of physical/chemical pretreatments, fungal cultures, and incubation methods were investigated to metabolize GLS into cell mass, CO2, or other non-toxic components. These treatments also served to hydrolyze canola meal fiber into carbohydrates which were then metabolized by the fungi into single cell protein. Solid-state incubation conditions were initially tested, since filamentous fungi are well adapted to grow at lower moisture levels, and this would potentially reduce contamination issues with bacteria. Flask trials were performed using 50% moisture, hexane extracted (HE) or cold pressed (CP) canola meal, with incubation for 168 h at 30ºC. On HE canola meal Trichoderma reesei (NRRL-3653) achieved the greatest increase in protein content (23%), while having the lowest residual levels of sugar (8% w/w) and GLS (0.4 μM/g). On CP canola meal T. reesei (NRRL-3653), Aureobasidium pullulans (NRRL-58522), and …

The Role Of Dksa In The Stringent Response In The Lyme Disease Spirochete Borrelia Burgdorferi, Britney Cheff

Graduate Student Theses, Dissertations, & Professional Papers

Borrelia burgdorferi, the bacterium that causes Lyme disease, is maintained in nature through an enzootic cycle that includes a tick vector and a vertebrate host. The bacterium is acquired by an Ixodes tick from an infected vertebrate. The bacterium alters its gene expression to adapt to different environments of the tick and vertebrate. Between tick feedings, B. burgdorferi must contend with nutrient stress. The stringent response is a physiological mechanism when bacteria switch from “thriving” to “surviving” mode in response to limited nutrient resources; it is mediated by an increase in the nucleotide alarmone guanosine penta- or tetraphosphate, abbreviated …

Heterotrophic And Autotrophic Contribution To Dinitrogen Fixation In The Gulf Of Aqaba, Eyal Rahav, Barak Herut, Margaret R. Mulholland, Natalia Belkin, Hila Elifantz, Ilana Berman-Frank

OES Faculty Publications

We evaluated the seasonal contribution of heterotrophic and autotrophic diazotrophy to the total dinitrogen (N₂) fixation in the photic zone of a pelagic station in the northern Gulf of Aqaba, Red Sea. N₂ fixation rates were highest during a Trichodesmium bloom in winter (0.7 nmol N l^-1 d^-1), decreased 7-fold 1 wk later throughout the upper 200 m (~0.1 nmol N l^-1) d^-1), and were significantly coupled with both primary and bacterial productivity. N₂ fixation rates were generally higher in the upper 200 m (~0.4 nmol N l^{-1 …}