Bacterial Infections and Mycoses Commons^™

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Usefulness Of The Captia Syphilis Igg Eia Test Method And Reverse Algorithm For Detection Of Syphilis Infection In A Public Health Setting, Patricia Armour

Theses and Dissertations

Syphilis, a systemic sexually transmitted disease, is on the rise in the US, with infection rates the highest recorded since 1994 according to the CDC. Useful laboratory testing is an important diagnostic tool for determining individual syphilis infection and preventing community-wide disease spread.

The purpose of this study was to determine the usefulness of a specific automated treponemal test method, the Captia^TM Syphilis IgG EIA, and the syphilis reverse algorithm interpretation for detecting syphilis infection among patients seeking care in a public health clinic. The study employed a retrospective, nonexperimental descriptive correlational design with data collected between 2012-2013 from …

The Role Of Pro-Inflammatory Mediators Ifnβ And Prostaglandin E2 In Suppression Of Innate Immunity To Listeria Monocytogenes, Michelle G. Pitts

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

As a foodborne pathogen, Listeria monocytogenes (Lm) encounters many barriers to invasion and dissemination in the host that may change the nature of host response. Lm has been most commonly studied using intravenous (i.v.) inoculation, however, a method that delivers a bolus of bacteria directly to the bloodstream. Thus, little is known about what systemic and local mediators are triggered during the natural course of infection and how these may impact susceptibility. Our laboratory used foodborne transmission of Lm in mice to assess whether the method of transmission and the specific organ microenvironment could affect infection-induced secretion of …

Characterization Of Different Molecular Markers For Identification Of Salmonella Enterica Serovar Typhi In Pakistani Population, Faizan Muttiullah, Fida Muhammad Khan, Fakhar-I- Abbas, Sabiha Shamim

Journal of Bioresource Management

Typhoid is caused by Salmonella enterica serovar Typhi that is usually diagnosed by using serologic and immuno-chromatographic techniques in developing counties including Pakistan, which is thought to be an unreliable diagnostic method. For accurate diagnosis we used molecular techniques to amplify 204 bp StyR-36 and 498 bp flagellin gene for the identification of Salmonella enterica serovar Typhi. This study was done on 58 individuals diagnosed positive of typhoid via serologic tests and 50 healthy individuals as a control group. Success rate of amplification for flagellin gene was 77.58% while that for StyR-36 gene was 68.97% showing that flagellin gene primer …

The Feoabc Locus Of Yersinia Pestis Likely Has Two Promoters Causing Unique Iron Regulation, Lauren O'Connor, Jacqueline D. Fetherston, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The FeoABC ferrous transporter is a wide-spread bacterial system. While the feoABC locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoABC in Yersinia pestis appears to be unique. None of the non-iron responsive transcriptional regulators that control expression of feoABC in other bacteria do so in Y. pestis. Another unique factor is the iron and Fur regulation of the Y. pestis feoABC locus occurs during microaerobic but not aerobic growth. Here we show that this unique iron-regulation is not due to a unique aspect of the Y. pestis …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Chat Expression In Chlamydia Muridarum-Infected Female Murine Genital Tract, Hallie Sartain

Undergraduate Honors Theses

Chlamydia trachomatis is the most prevalent agent of bacterial sexually transmitted infections in the world. However, a profuse number of cases are unreported, as the infection is often asymptomatic. Sequelae such as pelvic inflammatory disease, an increased risk of cervical cancer, premature birth, and perinatal infections in pregnant women can occur. Inflammation occurs in the body in response to infection or injury. Although inflammation can lead to some unwanted secondary effects, such as pain, it serves to return the body to homeostasis by restoring injured tissues and eliminating pathogens. One recently identified connection between the central nervous system and the …

Aspergillus Fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis Through Modulation Of Chitin Synthase Activity, Arsa Thammahong, Alayna K. Caffrey-Card, Sourabh Dhingra, Joshua J. Obar, Robert Cramer

Dartmouth Scholarship

Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslAand tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall …

Filamentous Fungal Carbon Catabolite Repression Supports Metabolic Plasticity And Stress Responses Essential For Disease Progression, Sarah R. Beattie, Kenneth Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna Caffrey-Carr, Chao Cheng

Dartmouth Scholarship

Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Williams Honors College, Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency …

Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP-induced mortality, serum tumor necrosis factor α (TNFα) levels, pulmonary myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1β messenger …

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 …

Changing Diagnostic Methods And Increased Detection Of Verotoxigenic Escherichia Coli, Ireland, Thomas Rice, Noreen Quinn, Roy D. Sleator, Brigid Lucey

Department of Biological Sciences Publications

The recent paradigm shift in infectious disease diagnosis from culture-based to molecular-based approaches is exemplified in the findings of a national study assessing the detection of verotoxigenic Escherichia coli infections in Ireland. The methodologic changes have been accompanied by a dramatic increase in detections of non-O157 verotoxigenic E. coli serotypes.

Fecal Transplant Vs Vancomycin For Recurrent Clostridium Diffile, Lauren M. Taylor, Todd E. Edwards

Physician Assistant Capstones, 2016 to 2019

Objective: To compare fecal transplant and vancomycin in the treatment of recurrent clostridium difficile to determine which has the higher cure rate. Design: Systematic literature review. Methods: Pubmed, Google Scholar, and TRIP database using the search terms “recurrent clostridium difficile.” Filters were implemented in the Pubmed database including: randomized control trials, English, and published in the past 5 years. Records were screened for RCT with fecal transplant and full-text. Results: van Nood et al. revealed an initial cure rate of 81% for the infusion group, and a re-treated cure rate of 94%, compared to the vancomycin alone group of 31% …

The Effect Of Increased Exposure Of Uvc Light On Human Skin Microbiota, T'Kylia S. Moss

Honors Theses

Many methods have been employed to prevent infections from opportunistic pathogens in immunocompromised individuals. Among these are the use of ultraviolet light (UV). In this study, UVC light, was found to have a deleterious effect on specific skin flora. Organisms tested included Acinetobacter baumanii, Candida albicans, Candida kefyr, Corynebacterium renale, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. Nutrient agar was used to cultivate most organisms. Blood agar was used for the cultivation of Streptococcus pyogenes and Enterococcus faecalis. Bacterial suspensions were made and utilized to plate each organism onto a set of 7 nutrient agar or …

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Characterization Of The Paracoccidioides Hypoxia Response Reveals New Insights Into Pathogenesis Mechanisms Of This Important Human Pathogenic Fungus, Patrícia De Sousa Lima, Dawoon Chung, Alexandre Melo Bailão, Robert A. Cramer, Célia Maria De Almeida Soares

Dartmouth Scholarship

Background: Hypoxic microenvironments are generated during fungal infection. It has been described that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental stress conditions including low oxygen tension; however nothing is known how Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis (PCM), an important mycosis in Latin America.

Design And Testing Of Novel Anthrax Vaccines Utilizing A Tobacco Mosaic Virus Expression System, Ryan C. Mccomb

KGI Theses and Dissertations

Anthrax is a potentially fatal disease caused by the bacteria Bacillus anthracis. Infection and disease occur after spores gain entry into the body, germinate into vegetative bacteria, and produce toxin. Bacillus anthracis spores have been engineered as bioweapons and have been used repeatedly in warfare and terrorism to inflict casualties in military and civilian populations. Currently, only one vaccine has been approved for prevention of anthrax in the United States. This vaccine is an undefined product that is difficult to produce, requires a long vaccination schedule, and is reactogenic. Efforts to make an improved anthrax vaccine are being pursued. …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …

Genetic Control Of Survival And Weight Loss During Pneumonic Burkholderia Pseudomallei (Bp) Infection, Felicia D. Emery

Theses and Dissertations (ETD)

Burkholderia pseudomallei (Bp) is a saprophytic, gram-negative aerobe and the causative agent of the disease melioidosis. Melioidosis is an infectious disease that occurs in humans and animals and is prevalent in Southeast Asia, northern Australia and other tropical areas. Transmission occurs through direct contact with the organism via ingestion, inhalation, or through open wounds and skin abrasions. Clinical presentation is extremely variable and can range from acute septicemia with bacterial dissemination to distant sites, to an isolated pulmonary infection. Treatment of melioidosis can be problematic because it is often difficult to diagnose and Bp is resistant to a diverse group …

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

Prevalence Of Sepsis In Pediatric Populations, Brittany Barnes

Nursing Student Class Projects (Formerly MSN)

Sepsis and more specifically septic shock in the pediatric population is a diagnosis that is full of complexities. There are instances where a neutropenic oncology patient observes a better outcome than a previously healthy patient who is suffering from the same pathogen related sepsis. Sepsis is the 10th leading cause of death according to the Center for Disease Control and Prevention, and each year between 20,000 and 42,000 children are diagnosed with severe sepsis (Riley & Wheeler, 2012). Even with significant advances in medical treatment, sepsis is still associated with high morbidity and mortality rates. A retrospective study of patient …

Identifying Acute Organ Dysfunction As A Marker Of Severe Sepsis, Daniell Mcsweeney

Nursing Student Class Projects (Formerly MSN)

The current definition of sepsis is suspected or documented infection plus at least one systemic manifestation of infection. Severe sepsis has been defined as sepsis plus evidence of organ dysfunction. Identifying acute organ dysfunction is a marker of severe sepsis. This topic was chosen after witnessing a number a patients fall into septic shock before severe sepsis was diagnosed and treatment initiated. Diagnosis of severe sepsis is important for specific protocol to be implemented in a timely fashion. The current differentiation between sepsis and severe sepsis is evidence of organ dysfunction. There are many examples of organ dysfunction that are …

Lyme Disease, Jared Hostetler

Nursing Student Class Projects (Formerly MSN)

Lyme disease is the most common vector borne illness found in the United States. Each year 30,000 people are diagnosed with the disease, with many more cases going unreported (Centers for Disease Control and Prevention, 2015). The vector responsible for spreading the disease is the deer tick. The infection itself is caused by the spirochete Borrelia burgdorferi. This bacteria is transmitted through the saliva from the bite of a deer tick. Diagnosis can be challenging due to the fact that multiple systems of the body can be affected with different severities. Early diagnosis and treatment is critical in the prevention …

Lyme Disease: A Tick’S Risky Bite, Jana Keller

Nursing Student Class Projects (Formerly MSN)

Lyme Disease is a bacterial infection transmitted primarily by the deer tick and is commonly seen in the United States. It is an infectious disease caused by the bacterium Borrelia burgdorferi, which is a spirochete (Pearson, 2014). Lyme disease’s prevalence is confirmed by the Centers for Disease Control and Preventions whom estimates that 30,000 people per year are diagnosed with Lyme disease in the Unites States (Moore, 2015). It is imperative that primary health care workers (such as Nurse Practitioners) are familiar with this disease and the early signs and symptoms. If early signs and symptoms go unnoticed or misdiagnosed …

Tuberculosis, Lindsay Mackey

Nursing Student Class Projects (Formerly MSN)

Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis and mostly affects the lungs and sometimes other organs such as the kidneys, spine, and brain (Center for Disease Control and Prevention, 2015). In 2013, the CDC (2015) estimated that approximately 9 million people were infected with Mycobacterium tuberculosis worldwide and approximately 1.5 million deaths were a result of TB. Tuberculosis is an airborne infection which can be spread through the air from an infected individuals cough, sneeze, or speech. Individuals infected with TB can either have latent or active stage. Latent TB is when an individual becomes infected …

Sepsis & Emergency Management, Sharon Herndon

Nursing Student Class Projects (Formerly MSN)

Sepsis is a potentially life-threatening complication of an infection and a leading cause of death in the United States (Cawcutt & Peters, 2014). Sepsis is a systemic inflammatory response syndrome (SIRS) to invading microorganisms. Sagy, Al-Qaquu, and Kim (2013) define sepsis in three categories. “Sepsis” would be defined as the presence of infection along with other general systemic signs and symptoms. “Severe Sepsis” would be defined as sepsis complicated by at least one organ dysfunction, and “Septic Shock” would be defined as severe sepsis with acute circulatory failure that may be characterized by persistent arterial hypotension unexplained by other causes. …