Diseases Commons^™

Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock

Katherine A. Fitzgerald

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that …

Structural And Molecular Analysis Of A Protective Epitope Of Lyme Disease Antigen Ospa And Antibody Interactions, Shivender Shandilya, Nese Kurt Yilmaz, Ejemel Monir, Andrew Sadowski, William D. Thomas, Mark S. Klempner, Celia A. Schiffer, Yan Wang

Celia A. Schiffer

The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease. Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 based on computational predictions on …

Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill

Neal Silverman

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing approximately 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, …

Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

In introducing the infectious disease focus for this edition of the Journal of Patient-Centered Research and Reviews, the author describes the unsolved mysteries surrounding the dimorphic fungus Blastomyces and the related pathogenesis of pulmonary blastomycosis.

Clinical Approach To Nonresponsive Pneumonia In Adults Diagnosed By A Primary Care Clinician: A Retrospective Study, Kiley B. Vander Wyst, Jessica J. F. Kram, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Purpose

Community-acquired pneumonia (CAP) is commonly diagnosed in the primary care setting. Management of nonresponsive pneumonia (NRP), i.e. failure to respond to CAP treatment, is not clearly understood. The purpose of this study was to describe the initial work-up and treatment of CAP in the ambulatory primary care setting and to determine relative proportion of, diagnostic approach to and treatment of NRP.

Methods

We retrospectively studied adult patients diagnosed with CAP within our large, integrated health care system from October 2006 through July 2013. Cases were defined as patients with CAP who worsened after 4 days, or did not improve …

Geodemographic Features Of Human Blastomycosis In Eastern Wisconsin, Megan E. Huber, Dennis J. Baumgardner, Jessica J. F. Kram, Melissa A. Lemke

Dennis J. Baumgardner, MD

Purpose

Blastomycosis is an endemic fungal infection. In rural northern Wisconsin, blastomycosis cases are associated with certain environmental features including close proximity to waterways. Other studies have associated blastomycosis with particular soil chemicals. However, blastomycosis also occurs in urban and suburban regions. We explored the geodemographic associations of blastomycosis cases in the more urban/suburban landscape of eastern Wisconsin.

Methods

We conducted a retrospective study of 193 laboratory-identified blastomycosis cases in a single eastern Wisconsin health system, 2007–2015. Controls were 250 randomly selected cases of community-diagnosed pneumonia from a similar time period. Geographic features of home addresses were explored using Google …

Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

A number of fungal pathogens that may result in a variety of human diseases are found in residential homes and yards. The growth of these microscopic fungi is often favored by particular characteristics of the dwelling and nearby outdoor environment. Evolved virulence factors or increased ability of specific fungi to grow in diverse, and sometimes harsh, microenvironments presented by the domestic environment may promote growth and pathogenesis. Infection may occur by inhalation or direct inoculation and include endemic fungi in addition to opportunistic or emerging species. Systemic or locally aggressive fungal infections are particularly likely and may be life-threatening in …

Geographic Distribution Of Maternal Group B Streptococcus Colonization And Infant Death During Birth Hospitalization: Eastern Wisconsin, Jessica J. F. Kram, Dennis J. Baumgardner, Kiley B. Vander Wyst, Melissa A. Lemke

Dennis J. Baumgardner, MD

Purpose

Maternal group B Streptococcus (GBS) can be transmitted from a colonized mother to newborn during vaginal delivery and may or may not contribute to infant death. This study aimed to explore the geographic distribution and risk factors of maternal GBS colonization and infant death during birth hospitalization.

Methods

We retrospectively studied mothers with live birth(s) in a large eastern Wisconsin hospital system from 2007 through 2013. Associations between maternal and neonatal variables, GBS colonization and infant death were examined using chi-squared, Mann-Whitney U and t-tests. Multivariable logistic regression models also were developed.

Results

Study population (N = 99,305) had …