Bacterial Infections and Mycoses Commons^™

Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott

Theses and Dissertations--Molecular and Cellular Biochemistry

The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation …

What Are The Barriers And Facilitators To Nurses’ Utilization Of A Nurse Driven Protocol (Ndp) For Indwelling Urinary Catheter (Iuc) Removal?, Brenda Clark

Interprofessional Research and Innovations Council

What are the barriers and facilitators to Nurses’ utilization of a Nurse Driven Protocol (NDP) for Indwelling Urinary Catheter (IUC) removal?

By Brenda Clark, BSN, RN, CMSRN

Background: Urinary tract infections (UTIs) are recognized as a major cause of morbidity and mortality in hospitalized patients; 80% of UTIs are related to using indwelling urinary catheters.

Reducing these infections is recognized as a National Patient Safety Goal (NPSG) by the Joint Commission; the American Nurses Association (ANA) has classified catheter associated urinary tract infections (CAUTIs) as one of the nurse-sensitive indicators that reflect the quality of nursing care. Centers for Medicare …

Characterizing The Role Of Cpsa In Mycobacterial Pathogenesis, Amir Hassan

Undergraduate Research Symposium Posters

Mycobacterium tuberculosis infects one-third of the world’s population and causes an estimated 2 million deaths per year, more than any other single bacterial pathogen. The inadequacies of existing tuberculosis therapies demand the discovery of novel agents to treat M. tuberculosis infection, which requires mechanistic insight into the pathways involved in mycobacterial pathogenesis. We identified an unanticipated role of the M. tuberculosis protein CpsA in preventing phago-lysosome fusion by host macrophages, resulting in enhanced intracellular survival of bacteria within the host. Strains of M. tuberculosis lacking cpsA are severely attenuated in both macrophage and mouse models, thus establishing CpsA as a …

Nitrosative Stress Sensing In Porphyromonas Gingivalis: Structure And Function Of The Heme Binding Transcriptional Regulator Hcpr, Benjamin R. Belvin

Theses and Dissertations

Porphyromonas gingivalis, a Gram negative anaerobe implicated in the progression of periodontal disease, is capable of surviving and causing infection despite high levels of reactive nitrogen species found in the oral cavity due to its efficient nitrosative stress response. HcpR is an important sensor-regulator that plays a vital step in the initiation of the nitrosative stress response in many Gram negative anaerobic bacteria. We employ a combination of X-ray crystallography, SAXS, resonance Raman spectroscopy, UV-Vis spectroscopy, and molecular biology techniques to better understand this key regulator. Knockout of the hcpR gene in W83 P. gingivalis results in the inability of …

Orientia Tsutsugamushi Secretes Two Ankyrin Repeat-Containing Effectors Via A Type 1 Secretion System To Inhibit Host Nf-Κb Function, Sean M. Evans

Theses and Dissertations

Scrub typhus is a potentially fatal infection that threatens one billion persons in the Asia-Pacific region and is caused by the obligate intracellular bacterium, Orientia tsutsugamushi. How this organism facilitates its intracellular survival and pathogenesis is poorly understood. Intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) into the host cell to modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank libraries as well as Type 1 and Type 4 secretion systems (T1SS and T4SS), which are expressed during infection. In …

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Purpose

The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens(CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression.

Methods

P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured …

Fluoride Varnish Application In The Pediatric Population, Ellen Gnaedinger

Doctor of Nursing Practice (DNP) Projects

Purpose: The United States (U.S.) has a persistent problem of dental caries in primary teeth with a greater prevalence of dental caries found in minority and poor children. The majority of children in the U.S. experience dental caries in their primary teeth by age eight. This problem could be addressed by primary care providers applying fluoride varnish (FV) to children's teeth starting at the age of primary tooth eruption. The causes of dental caries in children’s primary teeth are multifactorial and therefore require multiple interventions. Around the world providers are utilizing FV as an effective and easily administered strategy. This …

Life-Threatening Hypercalcemia During Prodrome Of Pneumocystis Jiroveci Pneumonia In An Immunocompetent Infant, Judith Sebestyen Vansickle, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Severe hypercalcemia in infants is usually attributed to genetic etiologies and less commonly to acquired ones. An 8-week-old girl presented with failure to thrive, mild respiratory distress, and life-threatening hypercalcemia (23.5 mg/dL). Serum 1,25(OH)2-D) level was elevated and parathyroid hormone undetectable. Evaluation for genetic mutations and malignant etiologies of hypercalcemia was negative. Treatment with intravenous hydration, loop diuretic, and calcitonin failed to correct the hypercalcemia, which was subsequently controlled with bisphosphonate therapy. Due to progressive respiratory deterioration, a bronchopulmonary lavage was done on day 17 of her hospitalization disclosing Pneumocystis jiroveci infection. The subsequent immunological investigation showed no abnormalities. She …

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 …

Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer

Undergraduate Honors Thesis Collection

Tuberculosis (TB) is a highly infectious respiratory disease contracted through the inhalation of Mycobacterium tuberculosis. Serine hydrolases are abundant in M. tuberculosis and serve as a model for studying the inhibition of TB. Rv0045c is an example of such with little known regarding its biological function. Rv0045c was exposed to methanol, ethanol, isopropanol, or glycerol and the effects of varying concentration of these alcohols on the catalytic efficiency and thermal stability of the enzyme was determined. The thermal stability of Rv0045c was found to decrease with concentration of methanol, ethanol, or isopropanol. The opposite was true of the thermal stability …

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 …

Geographical Incidence Of Antimicrobial Resistant Gonorrhea, Christofer A. Rodriguez

Master's Projects and Capstones

Evolving throughout the last century, Gonorrhea has become a superbug, becoming difficult to treat. As the second most commonly reported notifiable disease, gonorrhea rates have been increasing, despite efforts in prevention and treatment. Populations at risk are mainly MSM and FSW. In 2015, men’s gonorrhea rates in the United States were higher compared to women, at 140.9 and 107.2 per 100,000 population, respectively. Illinois has consecutively had higher rates of infection compared to the US, at 133.5 per 100,000 population compared to the US rate of 123.9 per 100,000 population. The surveillance of gonococcal isolate resistance to current antimicrobials began …

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3%) cases …

Xpert Mtb/Rif Assay Shows Faster Clearance Of Mycobacterium Tuberculosis Dna With Higher Levels Of Rifapentine Exposure., A Jayakumar, R M Savic, C K Everett, Debra Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid

Medicine Faculty Publications

The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity …

Intravenous Versus Oral Antibiotics For Postdischarge Treatment Of Complicated Pneumonia., Samir S. Shah, Rajendu Srivastava, Susan Wu, Jeffrey D. Colvin, Derek J. Williams, Shawn J. Rangel, Waheeda Samady, Suchitra Rao, Christopher Miller, Cynthia Cross, Caitlin Clohessy, Matthew Hall, Russell Localio, Matthew Bryan, Gong Wu, Ron Keren, Pediatric Research In Inpatient Settings Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes.

METHODS: This multicenter retrospective cohort study included children ≥2 months andadministration, classified as PICC or oral. The primary outcome was treatment failure. Secondary outcomes included PICC complications, adverse drug reactions, other related revisits, and a composite of all 4 outcomes, termed "all related revisits."

RESULTS: Among 2123 children, 281 (13.2%) received antibiotics …

Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen

Electronic Theses and Dissertations

Background: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases on the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of …

Epidemiology And Impact Of Campylobacter Infection In Children In 8 Low-Resource Settings: Results From The Mal-Ed Study, Shahida Qureshi, Aneeta Hotwani, Sadia Shakoor, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Zulfiqar Ahmed Bhutta, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life.
Methods: Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter Stool and blood samples were assayed for markers of intestinal permeability and inflammation.
Results: A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter We describe a high …

Tb Screening Guidelines For Transitional Care Unit, Caleb E. Newcomer

Scholars Week

The basis of this research was the formation of new TB screening and risk assessment guidelines on a Transitional Care Unit within a medical center. Current evidence-based research studies helped to guide the recommendations for the policy changes based on their results and findings. The most pertinent policy changes are the treatment offered for patients suspected with HIV, the rigorous use of the Risk Assessment Tool, and BAMT testing for TB.