Immunology and Infectious Disease Commons^™

Rapid Typing Of Mannheimia Haemolytica Major Genotypes 1 And 2 Using Maldi-Tof Mass Spectrometry, John Dustin Loy, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Genotype 2 M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate genotype 2 strains in veterinary diagnostic laboratories.

Cytolytic Toxin Production By Staphylococcus Aureus Is Dependent Upon The Activity Of The Protoheme Ix Farnesyltransferase, Emily Stevens, Maisem Laabei, Stewart Gardner, Greg A. Somerville, Ruth C. Massey

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use …

Branched Chain Α-Ketoacid Dehydrogenase Kinase 111–130, A T Cell Epitope That Induces Both Autoimmune Myocarditis And Hepatitis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A. Uzal, Jennifer L. Strande, Gustavo A. Delhon, Jean-Jack Riethoven, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread.

Methods: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKD_k) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.

Results: We demonstrate that BCKD_k protein contains at least nine immunodominant epitopes, three of which, BCKD_k 71–90, BCKD_k 111–130 and BCKD_k 141–160, …

Mechanistic Understanding Of N-Glycosylation In Ebola Virus Glycoprotein Maturation And Function, Bin Wang, Yujie Wang, Dylan A. Frabutt, Xihe Zhang, Xiaoyu Yao, Dan Hu, Zhuo Zhang, Chaonan Liu, Shimin Zheng, Shi-Hua Xiang, Yong-Hui Zheng

School of Veterinary and Biomedical Sciences: Faculty Publications

The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP₁ and the fusion-mediating GP₂ subunits and incorporated into virions to initiate infection. GP₁ and GP₂ form heterodimers that have 15 or two N-glycosylation sites (NGSs), respectively. Here we investigated the mechanism of how N-glycosylation contributes to GP expression, maturation, and function. As reported before, we found that, although GP₁ NGSs are not critical, the two GP₂ NGSs, Asn⁵⁶³ and Asn⁶¹⁸, are essential for GP function. Further analysis uncovered that Asn⁵⁶³ and Asn^{618 …}

A Novel Role Of Silibinin As A Putative Epigenetic Modulator In Human Prostate Carcinoma, Ioannis Anestopoulos, Aristeidis P. Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I. Panayiotidis, David J. Kroll, Aglaia Pappa

School of Veterinary and Biomedical Sciences: Faculty Publications

Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, …

Ccpa Affects Infectivity Of Staphylococcus Aureus In A Hyperglycemic Environment, Markus Bischoff, Bodo Wonnenberg, Nadine Nippe, Naja J. Nyffenegger-Jann, Meike Voss, Christoph Beisswenger, Cord Sunderkotter, Virginie Molle, Quoc Thai Dinh, Frank Lammert, Robert Bals, Mathias Herrmann, Greg A. Somerville, Thomas Tschernig, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA). Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections. In hyperglycemic individuals, the bacterium Staphylococcus aureus causes serious, life-threatening infections. The importance of CcpA in regulating carbon catabolite repression in S. aureus suggests it may be important for infections in hyperglycemic individuals. To test this suggestion, hyperglycemic non-obese diabetic (NOD; blood glucose level ≥20 mM) mice were challenged with the …

Pseudoscorpions Of The Family Cheiridiidae (Arachnida: Pseudoscorpiones) Recovered From Burial Sediments At Pachacamac (500–1,500ce), Peru, Johnica J. Morrow, Livia Taylor, Lauren Peck, Christian Elowsky, Lawrence Stewart Owens, Peter Eeckout, Karl Reinhard

Karl Reinhard Publications

Fragmented remains of pseudoscorpions belonging to the family Cheiridiidae (Arachnida, Pseudoscorpiones) were recovered from Ychsma polity (c. AD 1000–1475) burial sediments from Pachacamac, Peru. Sediments from 21 burials were examined following rehydration in 0.5% trisodium phosphate for 48 h and subsequent screening through a 250 lm mesh. Materials larger than 250 lm were surveyed for the presence of arthropods. A total of two samples contained pseudoscorpion fragments, which were collected and quantified to determine the minimal number of pseudoscorpions present per gram of each sample. Following quantification, pseudoscorpion specimens were imaged utilizing confocal laser scanning microscopy (CLSM) to assist with …

Defining The Risk Of Zika And Chikungunya Virus Transmission In Human Population Centers Of The Eastern United States, Carrie A. Manore, Richard S. Ostfeld, Folashade B. Agusto, Holly Gaff, Shannon L. Ladeau

Biological Sciences Faculty Publications

The recent spread of mosquito-transmitted viruses and associated disease to the Americas motivates a new, data-driven evaluation of risk in temperate population centers. Temperate regions are generally expected to pose low risk for significant mosquito-borne disease; however, the spread of the Asian tiger mosquito (Aedes albopictus) across densely populated urban areas has established a new landscape of risk. We use a model informed by field data to assess the conditions likely to facilitate local transmission of chikungunya and Zika viruses from an infected traveler to Ae. albopictus and then to other humans in USA cities with variable human …

Role Of The Interleukin-22 And Stat3 Signaling Pathway In Gut Barrier Maintenance Following Intoxication And Burn Injury, Adam M. Hammer

Dissertations

More than half of patients admitted to burn centers for treatment have measurable alcohol levels in their blood. Intoxication that precedes a traumatic burn injury leads to worsened patient outcomes, including higher rates of infection and sepsis. The intestines harbor the largest concentration of bacteria in the human host. Any disruption of the intestinal barrier as a result of intoxication and burn injury could contribute to infection and/or sepsis from gut-derived microbes. Previous work has demonstrated that the intestinal barrier becomes leaky, and that administration of interleukin-22 (IL-22) significantly reduces gut barrier leakiness following alcohol and burn injury. However, the …

Vaccination Status And Factors For Non- Vaccination In Children At A Tertiary Care Hospital, Shiyam Sunder Tikmani, Tufail Soomro, Sumera Aziz Ali

Community Health Sciences

Immunization is a very effective strategy to prevent against common infectious disease. The objectives of the study were to determine the immunization status and reasons for non-vaccination of children coming to Civil Hospital Sukkur. This cross-sectional study was conducted pediatric OPD at Civil Hospital Sukkur from January 1, 2013, to June 30, 2013. Parents of children under five years of age brought their child to Outpatient Department of Civil Hospital Sukkur for any illness were asked to participate in the study. Parents who gave informed consent were included in the study. Data were collected using a small questionnaire by the …

Novel Possibilities For The Treatment And Prevention Of Cutaneous Leishmaniasis, Eva A. Iniguez

Open Access Theses & Dissertations

Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniasis, which affect millions of people worldwide. Cutaneous leishmaniasis (CL) is mainly caused by either Leishmania major or L. tropica parasites, which produce localized cutaneous ulcers, often leading to scarring and social stigma. Currently, the disease has reached hyperendemicity levels in the Middle East due to conflict and human displacement and is one the most common forms of the disease in the Old World. Furthermore, the first choice of treatment in that region continues to be pentavalent antimonials, which are costly and highly toxic, and current vector control …

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 …

Why We Still Need To Worry About Bees, Meaghan Lee Callaghan

Capstones

American honey bees, and other native bee species, are still in decline, though the specter of colony collapse disorder may be fading behind us. Colony decline, the loss of bees overwinter experienced across the country at a quarter to third lost per hive (sometimes more), is now expected. Losses can include those from colony collapse disorder. The author discusses the different causes for colony decline and speaks to bee health scientists and local beekeepers. Read more at: http://www.meaghanleecallaghan.com/capstone/index.html

Staphylococcus Aureus Biofilms Interfere With Macrophage Antimicrobial Responses Through Differential Gene Regulation, Toxin Production, And Purine Metabolism, Tyler D. Scherr

Theses & Dissertations

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that is a leading cause of both nosocomial and community-associated infections. Armed with a myriad of virulence factors and the propensity to form a biofilm on native tissues and implanted medical devices alike, S. aureus infections represent a very real public health threat, the treatment of which results in an excessive economic burden. S. aureus biofilm infections are notoriously recalcitrant to antibiotic therapy and adept at evading and neutralizing the host immune antimicrobial response. Previous studies from our laboratory have shown that S. aureus biofilms are able to cause persistent …

Role Of Cbl-Family Ubiquitin Ligases As Critical Negative Regulators Of T Cell Activation And Functions, Benjamin Goetz

Theses & Dissertations

Adaptive T cell immunity is essential for defense against foreign antigens and immune surveillance against cancer. Tight regulation of T cell activation is required to avoid autoimmunity to self-antigens or protracted inflammation after foreign antigens are cleared. Incomplete or inappropriate stimulation leads to an active shutdown of T cell activation called anergy. The Casitas B-lineage Lymphoma (CBL)-family of ubiquitin ligases (E3s) are essential negative regulators of T cell activation that impinge on thymic selection as well as anergy induction programs. Single gene studies show that CBL is critical during T cell development while CBL-B plays an essential role in peripheral …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

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 …

Repurposing Non-Antimicrobial Drugs To Treat Multi-Drug Resistant Bacterial And Fungal Infections, Shankar Thangamani

Open Access Dissertations

Bacterial and fungal resistance to conventional antimicrobials is a burgeoning global health epidemic that necessitates urgent action. Even more alarming, the development of new antimicrobials to treat these multidrug-resistant pathogens has not kept pace with the rapid emergence of resistance to current antimicrobials. Antimicrobial drug development through the traditional de novo process is a risky venture given the significant financial and time investment required by researchers and limited success rate of translating these compounds to the clinical setting. This has led researchers to mine existing libraries of clinical molecules in order to repurpose old drugs for new applications (as antimicrobials). …

The Effects Of Dietary Probiotic Inclusion On Skeletal Health Of Poultry And Its Possible Mechanisms, Feifei Yan

Open Access Dissertations

Probiotics are live microorganisms which may confer health benefits on the host when administered in appropriate amounts. Numerous studies have shown that probiotics improve bone health in humans and rodents with less information available on the skeletal health of avians given probiotics. The objective of this study was to determine the effects of probiotic supplementation on bone health of egg-laying and meat-type chickens. Dietary supplementation of a multi-species based probiotic reduced the percentage of shell-less eggs beginning at 4 wk following treatment and increased tibial and femoral bone mineral density in egg-laying hens at 7 wk post-treatment. Similarly, bone mineralization …