Bacterial Infections and Mycoses Commons^™

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Toll-Like Receptors 2 And 9 Are Important For Innate Immune Cell Activation And Recruitment In Hypersensitivity Pneumonitis, Kelly J. Andrews

Theses and Dissertations (ETD)

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalation of environmental antigens. The disease is characterized by alveolitis and granuloma formation; however, some patients develop chronic HP (CHP), a restrictive lung disease characterized by fibrosis. Previous studies revealed that neutrophils are recruited into the lung via a MyD88- dependent pathway and regulate disease severity through cytokine production. Toll-like receptors (TLRs) 2 and 9 recognize conserved molecular patterns present in bacteria, and signal through the adaptor molecule MyD88. The goal of my project is to investigate the role of TLRs 2 and 9 in the pathogenesis of HP …

Electrostatic Spray Application Of Food-Grade Organic Acids And Plant Extracts To Decrease Escherichia Coli O157:H7 And Salmonella Typhimurium On Select Produce, Leighanna Maeree Massey

Graduate Theses and Dissertations

Both consumers and suppliers have been negatively affected by an increase in foodborne pathogens contaminating fruits. Consequently, there is a need for the development of more efficient antimicrobials and application techniques to decrease contamination. Natural preservatives such as organic acids and plant extracts have demonstrated promising results in decontaminating produce. In addition, the effectiveness of such preservatives may be enhanced by the use of an electrostatic sprayer. The objective of this research was to determine the combinations and concentrations of organic acids and plant extract that were able to reduce Salmonella Typhimurium (ST) and Escherichia coli O157:H7 (EC) inoculated fruits …

Phenotypic, Physiological And Growth Interactions Among Salmonella Serovars, Juliany Rivera Calo

Graduate Theses and Dissertations

This thesis consists of four research parts: a literature review that covers Salmonella spp., one of the more prominent foodborne pathogens that represents a major risk to humans (chapter 1). Understanding the growth of Salmonella serovars and strains is an important basis for more in depth research. In this case we studied a) the aerobic and anaerobic growth responses of multiple strains from six different serovars, b) how the spent media from different serovars, more importantly S. Heidelberg, affect the growth of S. Typhimurium, and c) determined whether or not two different serovars undergo competitive interactions when they were …

Effect Of Electrostatic Spraying Of Food-Grade Organic And Inorganic Acids, And Grape Seed Extract On Salmonella Typhimurium And Escherichia Coli O157:H7 On Spinach And Iceberg Lettuce, Vijayalakshmi Ganesh

Graduate Theses and Dissertations

The safety of fresh produce is often challenged by the sporadic incidences of outbreaks owing to Salmonella Typhimurium (S.T.) and Escherichia coli O157:H7 (E.c.). Washing and current disinfection strategies do not completely decontaminate leafy greens such as spinach and iceberg lettuce. Therefore, more effective treatments are essential to ensure the microbial safety of the produce at the selling point. Here, a multiple hurdle approach was applied: (1) Natural antimicrobials - organic acids (malic, lactic and tartaric acids; MA, LA, TA, respectively) and plant extract (grape seed extract, GSE) and (2) Application method - Electrostatic spraying, was …

Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek

Theses and Dissertations (ETD)

Candida albicans is the most prevalent human fungal pathogen, found as a commensal organism in the mucosa, gastrointestinal, and urogenital tracts of humans. This pathogenic fungus causes a wide spectrum of diseases, including the mucosal infection oropharyngeal candidiasis (OPC) which frequently effects patients with human immunodeficiency virus (HIV). The azole antifungals (such as fluconazole) are the most widely used and important ergosterol biosynthesis inhibitors (EBIs) for the treatment of Candida infections, including OPC. However, the azoles are fungistatic against C. albicans and therefore have limited efficacy against this organism, especially for immunocompromised patients. In C. albicans, the transcription factor Upc2 …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Multi-Criteria Decision Analysis As An Innovative Approach To Managing Zoonoses: Results From A Study On Lyme Disease In Canada, Cécile Aenishaenslin, Valérie Hongoh, Hassane D. Cissé, Anne Gatewood Hoen

Dartmouth Scholarship

ackground: Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for …

Pseudomonas Aeruginosa Exotoxin Y-Mediated Tau Hyperphosphorylation Impairs Microtubule Assembly In Pulmonary Microvascular Endothelial Cells, Ron Balczon, Nutan Prasain, Cristhiaan Ochoa, Jason Prater, Bing Zhu, Mikhail Alexeyev, Sarah Sayner, Dara W. Frank, Troy Stevens

University Faculty and Staff Publications

Pseudomonas aeruginosa uses a type III secretion system to introduce the adenylyl and guanylyl cyclase exotoxin Y (ExoY) into the cytoplasm of endothelial cells. ExoY induces Tau hyperphosphorylation and insolubility, microtubule breakdown, barrier disruption and edema, although the mechanism(s) responsible for microtubule breakdown remain poorly understood. Here we investigated both microtubule behavior and centrosome activity to test the hypothesis that ExoY disrupts microtubule dynamics. Fluorescence microscopy determined that infected pulmonary microvascular endothelial cells contained fewer microtubules than control cells, and further studies demonstrated that the microtubule-associated protein Tau was hyperphosphorylated following infection and dissociated from microtubules. Disassembly/reassembly studies determined that …

Antimycobacterial And Photosynthetic Electron Transport Inhibiting Activity Of Ring-Substituted 4-Arylamino-7-Chloroquinolinium Chlorides, Jan Otrevel, Pavel Bobal, Iveta Zadrazilova, Rodeney Govender, Matus Pesko, Stanislava Keltosova, Petra Koleckarova, Petr Marsalek, Ales Imramovsky, Aidan Coffey, Jim O'Mahony, Peter Kollar, Alois Cizek, Katarina Kralova, Josef Jampilek

Department of Biological Sciences Publications

In this study, a series of twenty-five ring-substituted 4-arylamino-7-chloroquinolinium chlorides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts and also primary in vitro screening of the synthesized compounds was performed against mycobacterial species. 4-[(2-Bromophenyl)amino]-7-chloroquinolinium chloride showed high biological activity against M. marinum, M. kansasii, M. smegmatis and 7-chloro-4-[(2-methylphenyl)amino]quinolinium chloride demonstrated noteworthy biological activity against M. smegmatis and M. avium subsp. paratuberculosis. The most effective compounds demonstrated quite low toxicity (LD₅₀ > 20 μmol/L) against the human monocytic leukemia THP-1 cell line within preliminary …

Comparison Of The Virulence Markers Of Helicobacter Pylori And Their Associated Diseases In Patients From Pakistan And Afghanistan, Javed Yakoob, Zaigham Abbas, Wasim Jafri, Muhammad W. Usman, Fatima Jafri, Safia Awan

Section of Gastroenterology

BACKGROUND/AIM: Helicobacter pylori is a Gram-negative bacteria, which is associated with development of gastroduodenal diseases. The prevalence of H. pylori and the virulence markers cytotoxin-associated gene A and E (cagA, cagE) and vacuolating-associated cytotoxin gene (vacA) alleles varies in different parts of the world. H. pylori virulence markers cagA, cagE, and vacA alleles in local and Afghan nationals with H. pylori-associated gastroduodenal diseases were studied.

PATIENTS AND METHODS:Two hundred and ten patients with upper gastrointestinal symptoms and positive for H. pylori by the urease test and histology were included. One hundred and nineteen were local nationals and 91 were Afghans. …

Multicenter Study Of High-Dose Daptomycin For Treatment Of Enterococcal Infections, Anthony M. Casapao, Ravina Kullar, Susan L. Davis, Donald P. Levine, Jing J. Zhao, Brian A. Potoski, Debra A. Goff, Christopher W. Crank, John Segreti, George Sakoulas, Sara E. Cosgrove, Michael J. Rybak

Internal Medicine Faculty Publications

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggests that daptomycin > 6mg/kg/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (> 6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two-hundred and forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by 49 (20%) Enterococcus faecalis and 21 (9%) Enterococcus spp., overall 204 (83%) were VRE. Enterococcal infections included bacteremia (173, 71%), intra-abdominal (35, …

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Dartmouth Scholarship

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac

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. …

Mycobacterium Bovis (Bovine Tuberculosis) Infection In North American Wildlife: Current Status And Opportunities For Mitigation Of Risks Of Further Infection In Wildlife Populations, Ryan S. Miller, Steven J. Sweeney

Zoonotics and Wildlife Disease: Publications

Mycobacterium bovis (M. bovis), the causative agent of bovine tuberculosis, has been identified in nine geographically distinct wildlife populations in North America and Hawaii and is endemic in at least three populations, including members of the Bovidae, Cervidae, and Suidae families. The emergence of M. bovis in North American wildlife poses a serious and growing risk for livestock and human health and for the recreational hunting industry. Experience in many countries, including the USA and Canada, has shown that while M. bovis can be controlled when restricted to livestock species, it is almost impossible to eradicate …

Effects Of Clostridium Difficile On The Human Immune Response, Mike Mcgovern

Honors Projects in Science and Technology

Clostridium difficile is a bacterium that is rapidly becoming a large issue in the medical community due to its tendency to infect hospital patients and its resistance to antibiotics. By studying the way in which the pathogen interacts with the human immune system, it is possible to better understand how the body naturally fights off the disease. This knowledge can allow medical professionals to develop treatments that can help curtail the infection before serious symptoms occur. Working under a grant program alongside Professors Kirsten Hokeness and Chris Reid, I was able to research the effects that exposure to the C. …

Calcium Phosphate Nanoparticles: A Future Therapeutic Platform For The Treatment Of Osteomyelitis?, Tejal A. Dasai, Vuk Uskoković

Pharmacy Faculty Articles and Research

No abstract provided.

Chlamydia Pneumoniae Infection Of Neuronal Cells Induces Changes In Calcium-Associated Gene Expression Consistent With Alzheimer’S Disease, Christopher Andrew Cappellini, Ahmad B. Cader, Keith G. Williams, Juliana Zoga, Susan T. Hingley

Scholarly Posters

Background and Significance: Previous studies have shown that cells infected with Chlamydia pneumoniae (Cpn) exhibit altered gene expression consistent with that observed in Alzheimer’s disease (AD). Furthermore, AD neurodegeneration has been linked to dysregulation of intracellular calcium and calcium-related processes. Therefore, we hypothesize that one mechanism by which pathogenesis evolves in AD is through infection-induced changes in expression of calcium-related genes. Objectives: To determine if infection of neuronal cells with Cpn alters expression of calciumrelated genes associated with neurodegeneration. Methods: SK-N-MC neuronal cells were infected with Cpn (AR39 strain; MOI=1) for 3 to 72 hours, then calcium-related genes were screened …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 1: Preparation And Drug Release, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the …

Osteogenic And Antimicrobial Nanoparticulate Calcium Phosphate And Poly-(D, L-Lactide-Co-Glycolide) Powders For The Treatment Of Osteomyelitis, Vuk Uskoković, Charles Hoover, Marija Vukomanović, Dragan P. Uskoković, Tejal A. Dasai, Charles Hoover, Marija Vukomanović, Dragan P. Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, …

Neisseria Oralis Sp. Nov., Isolated From Healthy Gingival Plaque And Clinical Samples, William J. Wolfgang, Teresa V. Passaretti, Reashma Jose, Jocelyn Cole, An Coorevits, Andrea N. Carpenter, Sherly Jose, Anita Van Landschoot, Jacques Izard, Donna J. Kohlerschmidt, Peter Vandamme, Floyd E. Dewhirst, Mark A. Fisher, Kimberlee A. Musser

Department of Food Science and Technology: Faculty Publications

A polyphasic analysis was undertaken of seven independent isolates of gram-negative cocci collected from pathological clinical samples from New York, Louisiana, Florida, and Illinois and healthy subgingival plaque from a patient in Virginia, USA. The 16S rRNA gene sequence similarity among these isolates was 99.7–100 %, and the closest species with a validly published name was Neisseria lactamica (96.9 % similarity to the type strain). DNA–DNA hybridization confirmed that these isolates are of the same species and are distinct from their nearest phylogenetic neighbor, N. lactamica. Phylogenetic analysis of 16S and 23S rRNA gene sequences indicated that the …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 2: Antibacterial And Osteoblastic Response, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time …

Efficacy Of Probiotics Lactobacillus Rhamnosus Gg And Saccharomyces Boulardii In The Treatment Of Antibiotic-Associated Diarrhea And Clostridium Diffiicile-Associated Disease, Estie Klugmann

The Science Journal of the Lander College of Arts and Sciences

Antibiotic therapy may cause serious side effects. Two disturbing effects of antibiotic administration are antibiotic-associated diarrhea and Clostridium difficile-associated disorder. Antibiotic-associated diarrhea occurs as a direct result of the normal flora destruction due to the antibiotics - which do not discriminate against pathogens or healthy forms of bacteria. C. diff disorder also occurs as an indirect result of antibiotic administration, because the destruction of the normal flora prevents people from having healthy bacteria to prevent disease. There have been studies conducted to determine if replacing the destroyed normal flora with probiotics, or beneficial microorganisms will prevent or treat these conditions. …