Infectious Disease Commons^™

Pyrimidine Pathway-Dependent And -Independent Functions Of The Toxoplasma Gondii Mitochondrial Dihydroorotate Dehydrogenase, Miryam Andrea Hortua Triana, Daniela Cajiao Herrera, Barbara H. Zimmermann, Barbara A. Fox, David Bzik

Dartmouth Scholarship

Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria. In Toxoplasma gondii, disruption of the first, fifth, or sixth step of de novo pyrimidine biosynthesis induced uracil aux- otrophy. However, previous attempts to generate uracil auxotrophy by genetically deleting the mitochondrion-associated DHODH of T. gondii (Tg DHODH) failed. To further address the essentiality of Tg DHODH, mutant gene alleles deficient in Tg DHODH activity were designed to ablate the enzyme activity. …

Performance Of Point-Of-Care Cd4 Testing Technologies In Resource-Constrained Settings: A Systematic Review And Meta-Analysis, Minh D. Pham, Paul A. Agius, Lorena Romero, Peter Mcglynn, David Anderson, Suzanne M. Crowe, Stanley Luchters

Population Health, East Africa

Background: Point-of-care (POC) CD4 testing increases patient accessibility to assessment of antiretroviral therapy eligibility. This review evaluates field performance in low and middle-income countries (LMICs) of currently available POC CD4 technologies.

Methods: Eight electronic databases were searched for field studies published between January 2005 and January 2015 of six POC CD4 platforms: PointCare NOW™, Alere Pima™ CD4, Daktari™ CD4 Counter, CyFlow® CD4 miniPOC, BD FACSPresto™, and MyT4™ CD4. Due to limited data availability, meta-analysis was conducted only for diagnostic performance of Pima at a threshold of 350 cells/μl, applying a bivariate multi-level random-effects modelling approach. A covariate extended model was …

An Unusual Pathogen Causing Native Valve Endocarditis., Aneela Hussain, Nosheen Nasir, Bushra Jamil

Department of Medicine

No abstract provided.

Human Metapneumovirus Induces Reorganization Of The Actin Cytoskeleton For Direct Cell-To-Cell Spread, Farah El Najjar, Nicolás Cifuentes-Muñoz, Jing Chen, Haining Zhu, Ursula J. Buchholz, Carole L. Moncman, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. …

Immune- And Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants Of Herpes Simplex Virus-Induced Generalized Infections And Acute Liver Failure, Zachary M. Parker, Tracy Jo Pasieka, George A. Parker, David A. Leib

Dartmouth Scholarship

The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR-/- mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR-/- (AG129) and wild-type (WT; 129SvEv) mice …

Early Haart Should Be Used For Treatment-Naive Hiv Patients With Pneumocystis Pneumonia, Maxwell L. Winkler

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Manzardo C, Esteve A, Ortega N, et al. Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort. Clin. Microbiol. Infect. 2013 July;19(7):646-653. doi: 10.1111/j.1469-0691.2012.03991.x

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5-fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. Ad5-R3 …

Effects Of Tcpb Mutations On Biogenesis And Function Of The Toxin-Coregulated Pilus, The Type Ivb Pilus Of Vibrio Cholerae, Yang Gao, Caitlyn A. Hauke, Jarrad M. Marles, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae is the etiological agent of the acute intestinal disorder cholera. The toxin-coregulated pilus (TCP), a type IVb pilus, is an essential virulence factor of V. cholerae. Recent work has shown TcpB is a large minor pilin encoded within the tcp operon. TcpB contributes to efficient pilus formation and is essential for all TCP functions. Here we have initiated a detailed, targeted mutagenesis approach to further characterize this salient TCP component. We have identified (thus far) 20 residues of TcpB, which affect either the steady state level of TcpB or alter one or more TCP functions. This study …

Two Cases Of Vibrio Infection And Sepsis In The Delaware Estuary, René Daniel, Md, Joseph Yoo, Md, Roberto Fratamico, Md, Robert Measley, Md

The Medicine Forum

INTRODUCTION

Vibrio is a genus of Gram-negative motile rods. Several species are pathogenic, including Vibrio vulnificus and Vibrio parahaemolyticus. The interest in this genus is due to its extreme virulence and often fatal outcomes. In healthy patients, these infections are typically self-limited; however, in immunocompromised and cirrhotic patients, infections can result in bacteremia, which has a high fatality rate1. Both pathogens may cause acute gastroenteritis, necrotizing wound infections, and if severe, subsequent bacteremia. In this report, we present two cases of Vibrio infections recently identified in the Delaware River Estuary that resulted in severe sepsis and, in one case, death.

Unexplained Recurrent Fevers And The Importance Of Inquiring About Occupation: A Case Report, Zachary Reese, Ms4, Poonam Maru, Do

The Medicine Forum

INTRODUCTION

Many different tick-borne diseases are identified in various geographical areas throughout the United States. Ixodes scapularis tick-borne diseases can present unique diagnostic challenges because of their constellation of vague symptoms. The Ixodes scapularis tick, more commonly known as the blacklegged tick, is responsible for three specific tick-borne infections: Lyme disease (Borellia burgdorferii), Babesiosis (Babesia microti), and Anaplasmosis (Anaplasma phagocytophilum) also known as human granulocytic anaplasmosis. Although these three tick-borne diseases are characteristically found in the New England area, the geographical distribution of the Ixodes tick has expanded to encompass much of the northeastern United States and even states in …

Oral Cryptococcosis In A Patient With Chronic Lymphocytic Leukemia, Sachin Patel, Maria Navas, Courtney Batt, Robin L.P. Jump

Faculty Scholarship

No abstract provided.

Cyclic Di-Gmp-Regulated Periplasmic Proteolysis Of A Pseudomonas Aeruginosa Type Vb Secretion System Substrate, Richard B. Cooley, T. Jarrod Smith, Wilfred Leung, Valerie Tierney, Bradley Borlee, George A. O'Toole, Holger Sondermann

Dartmouth Scholarship

We previously identified a second-messenger-regulated signaling system in the environmental bacterium Pseudomonas fluorescens which controls biofilm formation in response to levels of environmental inorganic phosphate. This system contains the transmembrane cyclic di-GMP (c-di-GMP) receptor LapD and the periplasmic protease LapG. LapD regulates LapG and controls the ability of this protease to process a large cell surface adhesin protein, LapA. While LapDG orthologs can be identified in diverse

A Survey Of Tuberculosis Infection Control Practices At The Nih/Niaid/Daids-Supported Clinical Trial Sites In Low And Middle Income Countries., Catherine Godfrey, Gail Tauscher, Sally Hunsberger, Melissa Austin, Lesley Scott, Jeffrey T. Schouten, Anne F. Luetkemeyer, Constance Benson, Robert Coombs, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement.

METHODS: A survey was developed that assessed IC activities in three domains: facility …

The Pseudomonas Aeruginosa Efflux Pump Mexghi-Opmd Transports A Natural Phenazine That Controls Gene Expression And Biofilm Development, Hassan Sakhtah, Leslie Koyama, Yihan Zhang, Diana K. Morales, Blanche Fields, Alexa Price-Whelan, Deborah Hogan

Dartmouth Scholarship

Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI-OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We …

Tobacco Cessation Treatment: Knowledge, Attitude And Practices Of Physician In Karachi, Pakistan: A Cross Sectional Study, Muhammad Naeem, Muhammad Irfan, Minaz Mawani, Zeeshan Waheed, Ahmed Suleman Haque, Ali Bin Sarwar Zubairi, Javaid Khan

Section of Pulmonary & Critical Care

Introduction: Tobacco smoking is a public health problem leading to substantial morbidity and mortality with around 80% of the deaths occurring in developing countries. Physician intervention has been shown to increase cessation rates. The study aims to assess knowledge, attitudes and practices of physicians in tobacco cessation treatment in Karachi Pakistan.

Methods: A descriptive cross sectional study was carried out between June to December 2013. All practicing physicians from Karachi were recruited. Survey questionnaire was distributed among randomly selected physicians after obtaining their consent. The study was approved by ethics review committee of The Aga Khan University Hospital.

Results: A …

A Survey And Analysis Of The American Public's Perceptions And Knowledge About Antibiotic Resistance, Rebecca R. Carter, Jiayang Sun, Robin L.P. Jump

Faculty Scholarship

Background. Little is known about the American public's perceptions or knowledge about antibiotic-resistant bacteria or antibiotic misuse. We hypothesized that although many people recognize antibiotic resistance as a problem, they may not understand the relationship between antibiotic consumption and selection of resistant bacteria. Methods. We developed and tested a survey asking respondents about their perceptions and knowledge regarding appropriate antibiotic use. Respondents were recruited with the Amazon Mechanical Turk crowdsourcing platform. The survey, carefully designed to assess a crowd-sourced population, asked respondents to explain "antibiotic resistance" in their own words. Subsequent questions were multiple choice. Results. Of 215 respondents, the …

Serratia Fonticola, Pathogen Or Bystander? A Case Series And Review Of The Literature, Roberto Viau, Robin L.P. Jump

Faculty Scholarship

Serratia fonticola is an unusual human pathogen, previously described primarily as causing skin and soft tissue infections following trauma. There is little information in the literature about its treatment or susceptibilities. We describe the case of a 67-year-old male with paraplegia who developed urosepsis due to S. fonticola. Blood and urine cultures obtained prior to the initiation of antimicrobials both grew S. fonticola. The patient completed a 15-day course of antimicrobials and had an uneventful recovery.We reviewed 17 other patients with clinical cultures positive for S. fonticola. Of these, 11 isolates were from the genitourinary system, most often as part …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …