Microbiology Commons^™

New World Mammarenaviral Hemorrhagic Fever Virus Determinants Of Infection And Disease, Brady T. Hickerson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Several New World mammarenaviruses (NWM) are able to cause life-threatening hemorrhagic disease in humans. These agents use human transferrin receptor 1 (hTfR1), the main protein involved in cellular uptake of iron, to infect cells. Furthermore, use of hTfR1 correlates with the ability of these viruses to cause severe disease in humans. The most prevalent pathogenic NWM is Jun√≠n virus (JUNV), which is the etiological agent of Argentine hemorrhagic fever (AHF).The pathogenesis of AHF is poorly understood. A cardinal feature of severe cases of AHF is a prolonged increase of serum interferon-a (IFN-a) concentration. This increase is hypothesized to play a …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky

Electronic Theses and Dissertations

Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Utility Of Molecular Tools For The Identification And Characterization Of Infectious Agents, Shih Keng Loong

Student Works (2020-2029)

Molecular tools involving nucleic acid sequence-based detection offer rapid, sensitive and specific identification of bacterial infections, all together instrumental in timely patient management and infection control. Analyses of DNA sequences played a pivotal role in the discovery of novel or uncommon bacterial pathogens. This method can be applied to detect and identify rare and potentially pathogenic bacterial infectious diseases emerging from the interactions between human, animal and the environment. In this study, the 16S rDNA sequencing demonstrated superior utility against the conventional phenotypic identification systems for the identification of rare pathogenic bacteria. Its inability to differentiate between certain bacterial species …

Deacetylation Of Hsd17b10 By Sirt3 Regulates Cell Growth And Cell Resistance Under Oxidative And Starvation Stresses., Lu Liu, Shuaiyi Chen, Miao Yu, Chenxu Ge, Mengmeng Ren, Boya Liu, Xin Yang, Thomas W Christian, Ya-Ming Hou, Junhua Zou, Wei-Guo Zhu, Jianyuan Luo

Department of Biochemistry and Molecular Biology Faculty Papers

17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) plays an important role in mitochondrial fatty acid metabolism and is also involved in mitochondrial tRNA maturation. HSD17B10 missense mutations cause HSD10 mitochondrial disease (HSD10MD). HSD17B10 with mutations identified from cases of HSD10MD show loss of function in dehydrogenase activity and mitochondrial tRNA maturation, resulting in mitochondrial dysfunction. It has also been implicated to play roles in the development of Alzheimer disease (AD) and tumorigenesis. Here, we found that HSD17B10 is a new substrate of NAD-dependent deacetylase Sirtuin 3 (SIRT3). HSD17B10 is acetylated at lysine residues K79, K99 and K105 by the acetyltransferase CBP, and the …

A Race Against Time: Reduced Azithromycin Susceptibility In Salmonella Enterica Serovar Typhi In Pakistan, Junaid Iqbal, Irum Fatima Dehraj, Megan E. Carey, Zoe A. Dyson, Denise Garrett, Jessica C. Seidman, Furqan Kabir, Senjuti Saha, Stephen Baker, Farah Naz Qamar

Department of Paediatrics and Child Health

Antimicrobial resistance is an ongoing issue in the treatment of typhoid fever. Resistance to first-line antimicrobials and extensively drug resistant (XDR) Salmonella Typhi isolates in Pakistan have left azithromycin as the only remaining effective oral treatment. Here, we report the emergence of organisms with a single point mutation in acrB gene, implicated in azithromycin resistance, in a S. Typhi isolate from Pakistan. The isolation of this organism is worrisome and highlights the significance of the introduction of typhoid conjugate vaccine in South Asia.
Importance: The emergence of XDR Salmonella Typhi in Pakistan has left azithromycin as the only viable oral …

Covid-19: In The Absence Of Vaccination – ‘Mask-The-Nation’, Roy D. Sleator, Steven Darby, Alan Giltinan, Niall Smith

Department of Biological Sciences Publications

“In the absence of a vaccine, or effective antiviral, one of our only remaining strategies for controlling COVID-19 is to physically block the spread of SARS-CoV-2 in the community”

Effect Of Botulinum Toxin Injection On Asymmetric Lower Face And Chin Deviation, Dongwook Kim, Ju-Hyun Park, Vittorio Favero, James Mah, Young-Soo Jung, Seong Taek Kim

Dental Medicine Faculty Research

The purpose of this study was to compare the efficacy of botulinum toxin (BoNT) in masseter muscle reduction depending on the amount of chin deviation. Exploring distinctive effects of BoNT relative to the characteristics of facial asymmetry will aid in planning and predicting treatment outcomes. Sixteen adult volunteers were classified into two groups according to the degree of menton deviation observed in posteroanterior cephalograms. Eight had a menton deviation of 3 mm or more and the other eight had less than 3 mm. A total of 25 Units of BoNT was injected into the unilateral masseter muscle of the prominent …

The Strengths, Weaknesses, Opportunities And Threats (Swot) Analysis Of The Severe Acute Respiratory Syndrome Coronavirus 2 Of Covid-19, Michael Oluyemi Babalola Ph.D

The University of Louisville Journal of Respiratory Infections

Introduction: SARS-CoV-2 is the etiologic agent of Coronavirus Disease 2019 (COVID-19), a highly contagious, emergent, acute, viral pneumonia that emanated sporadically in Wuhan, China, in December 2019. COVID-19 became a pandemic in February 2020, leading to 4,942,687 confirmed cases and over 321,987 deaths and grounding several economies around the world as of May 2020. Although global researchers, epidemiologists, virologists, and medical professionals rose steadily to contain the disease, in-depth knowledge of the virus and concerted efforts to combat it are still evolving. This research sought to elucidate the biological Strengths, Weaknesses, Opportunities, and Threats to SARS-CoV-2, with a view to …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans …

The Clinical Features Of Co-Circulating Dengue Viruses And The Absence Of Dengue Hemorrhagic Fever In Pakistan, Erum Khan, Dhani Prakoso, Kehkashan Imtiaz, Faisal Malik, Joveria Farooqi, Maureen T. Long, Kelli L. Barr

Department of Pathology and Laboratory Medicine

Dengue virus (DENV) is the most common and widespread arboviral infection worldwide. Though all four DENV serotypes cocirculate in nature, the clinicopathological framework of these serotypes is undefined in Pakistan. A cross-sectional, observational study was performed to document the circulation of various arboviruses in the Sindh region of Pakistan. Here we describe a population of patients diagnosed with DENV spanning a 2-year period. This study used an orthogonal system of NS1 antigen ELISA followed by RT-PCR for DENV detection and subtyping. A total of 168 NS1 positive patients were evaluated of which 91 patients were serotyped via RT-PCR. There was …

Contributions Of Gyra And Parc Mutations And Qnrs2 Acquisition To Ciprofloxacin Resistance In Aeromonas Veronii Hm21, Daniel J. Silverstein

Honors Scholar Theses

In recent years, ciprofloxacin resistant (CpR) Aeromonas veronii and A. hydrophila strains have been isolated from the wounds of patients receiving leech therapy. Genome comparisons of these CpR isolates revealed the presence of chromosomal mutations in gyrA and parC as well as the gain of qnrS2 on either a large, 34 kb, conjugatable, low-copy plasmid, pAv42, or on a small, 6.8 kb, high-copy plasmid, pAh1471. The minimum inhibitory concentration, MIC, for Cp of these clinical isolates ranged from 1 to ≥32 µg/mL and some harbored a qnrS2 containing plasmid. We wanted to assess the contributions of these factors in an …

Eggerthella Lenta Bacteraemia In Endometrial Adenocarcinoma - A Case Report From Pakistan, Tazeen Fatima, Rumina Hasan, Samia Tariq

Department of Pathology and Laboratory Medicine

We report a case of Eggerthella lenta bacteraemia. An elderly lady with metastasised endometrial adenocarcinoma presented with complaints of fever nausea vomiting and abdominal pain. CT scan of the abdomen showed enlarged liver with multiple metastatic lesions raising suspicion of small-bowel obstruction. Due to multiple comorbid conditions, surgery was contraindicated and she was treated empirically with meropenem and vancomycin. Blood culture received on admission grew Eggerthela lenta.

Seroprevalence, Biochemical Investigation And Risk Factor Assessment For Hbv & Hcv Infection In Hospital Based Patients Of Islamabad, Pakistan, Narmeen Adnan Rana, Bushra Munir, Nazeer Hussain, Nazia Imtiaz, Muhammad Asif Gondal Dr., Fahed Parvaiz Dr.

Journal of Bioresource Management

Viral hepatitis poses a serious threat to mankind. Hepatitis B and C Virus are blood borne pathogens that affect millions of individually globally. This study was conducted on a hospital-based population in Islamabad, Pakistan over a period of 4 months, utilizing ELISA as the diagnostic technique which suggested a higher seroprevalence rate for both HBV and HCV i.e. 2.07% and 8.24% respectively. A correlational analysis of the biochemical parameters of these individuals with HBV and HCV infection was carried out and the results indicated a positive correlation of HBV with Alkaline Phosphatase (ALP), HCV with Total Bilirubin (TBil) and both …

Using Short Chain Fatty Acids To Inactivate Pseudomonas Aeruginosa Biofilms, Stephen Lee

Dissertations and Theses

Abstract

Using Short Chain Fatty Acids to Disinfect Pseudomonas Aeruginosa Biofilms

by

Stephen Lee

Background

The study of bacteria typically focuses on the planktonic or free-living single-cell state that is purely cultured in a laboratory for subsequent growth with appropriate media. Although this traditional way of growing bacteria has been paramount to the understanding of bacterial behavior, physiology, and pathogenesis, bacteria rarely exist as pure cultures of planktonic growth forms in the natural habitat. Bacterial contamination of environmental surfaces, in the form of biofilms, is a prime public health problem and causes numerous infections within the general public. Biofilms are …

The Threat Of Antibiotic Resistance In Changing Climate, Aliyar Cyrus Fouladkhah, Brian Thompson, Janey Smith Camp

Agricultural and Environmental Sciences Faculty Research

As the earliest form of life, microorganisms have elaborate mechanisms for adapting to changes in environmental conditions.

Mathematical Modeling Of Gliding Motility And Its Regulation In Myxococcus Xanthus, Yirui Chen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Can Unconventional Immunomodulatory Agents Help Alleviate Covid-19 Symptoms And Severity?, Stephen W. Mamber, Steven Krakowka, Jeffrey L. Osborn, Lloyd Saberski, Ryan G. Rhodes, Albert E. Dahlberg, Sunthorn Pond-Tor, Kara Fitzgerald, Neal Wright, Sarah Beseme, John Mcmichael

Biology Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but …

Identifying Determinants Of Target Specificity In Two Related Bacterial Peptide Toxins, Andrew D. Holmes

Honors Thesis

Toxin-antitoxin (TA) systems were originally identified as two-component systems ensuring the stable inheritance of plasmids in bacterial populations. Recently, they have been identified on bacterial chromosomes where their functions remain mostly undefined. The par locus of E. faecalis plasmid pAD1 (par_pAD1) was the first TA system defined in a Gram-positive bacterium and a homolog encoded on the E. faecalis chromosome (par_EF0409) was later described. Related loci numbering in the hundreds have been identified throughout Gram-positive bacteria based on homology to the toxin of the system, Fst, and similarities in genetic organization and regulation. Despite …

Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara

Honors Theses

Described as one of the world’s worst pandemics, HIV (Human Immunodeficiency Virus) infects millions of people each year and is the cause for AIDS (Acquired Immunodeficiency Syndrome). Despite the development of vaccines for numerous infectious diseases such as polio, small pox, and influenza, a vaccine for HIV remains elusive due to the virus’s high mutation rate and ability to evade the immune system. HIV causes depletion of CD4+ lymphocytes, resulting in a weakened immune system. However, the development of a plasmid-based DNA vaccine approach may help revolutionize vaccine development for HIV due to its ability to confer cellular and humoral …

Influences Of Anti-Bd Bacteria On Amphibians And Their Microbiomes, Emme L. Schmidt

Honors Thesis

The fungal pathogen Batrochochytrium dendrobatidis (Bd) has been threatening amphibian populations across the globe. Recent work has discovered that bacteria isolated from certain populations of amphibians protect hosts from this pathogen. This project focuses on the anti-fungal mechanisms of Serratia marcescens, a species of bacteria isolated from a Costa Rican frog that dramatically inhibited Bd in culture. Wild-type and recombinant S. marcescens was introduced to the microbiomes of a live amphibian host, Acris blanchardi (Blanchard’s Cricket Frog) and then challenged with Bd to examine the protective effects of this bacteria. The experiment includes recombinant S. marcescens with …

The Effects Of Farnesol, A Quorum Sensing Molecule From Candida Albicans, On Alcaligenes Faecalis, Savannah Hutson

Undergraduate Honors Theses

Quorum sensing molecules have become a recent focus of study to learn if and how they can be used, both on their own and in conjecture with current antimicrobial methods, as a means of bacterial control. One such quorum sensing molecule is the sesquiterpene alcohol, Farnesol, which is synthesized and released by the fungus, Candida albicans. In most in-vivo cases, our laboratory has shown that Alcaligenes faecalis overtakes C. albicans, preventing its growth. However, as a way to counteract this inhibitory effect, Farnesol may be one way that Candida has found to fight back. In this study, we …

A Study Of The Polymicrobial Inhibitory Interactions Between Alcaligenes Faecalis And Staphylococcus Aureus, Blakeley Griffin

Undergraduate Honors Theses

Members of the Staphylococcus genus are found as a part of normal microflora in humans and can commonly be found on the skin or in the nasal cavity. However, these microorganisms can cause serious and life-threatening opportunistic infections when there is a break in the physical barrier of skin. These infections have become difficult to treat as resistant strains emerge, particularly Methicillin Resistant Staphylococcus aureus (MRSA). MRSA has become a commonly acquired nosocomial infection which is difficult to treat with conventional antibiotics of the blactam class. Even Vancomycin, a last resort antibiotic, has been ineffective on some infections. Furthermore, …

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

Second Messenger Cyclic-Di-Gmp Regulation In Acinetobacter Baumannii, Justin Deal

Undergraduate Honors Theses

Over time, “superbugs,” or bacteria that have become resistant to antibiotics, have become a great concern in modern medicine. Viable alternates are currently being looked into as effective and safe ways to prevent or treat infections caused by these superbugs. One such method is through the utilization of the second messenger molecule cyclic-di-GMP (c-di-GMP) that has been shown to regulate phenotypes within other bacteria that may control surface colonization in Acinetobacter baumannii. Through a series of experiments, the active enzymes that create c-di-GMP - diguanylate cyclases - and break down c-di- GMP - phosphodiesterases - have been inactivated in …

Draft Genome Sequences Of Two Extensively Drug-Resistant Strains Of Acinetobacter Baumannii Isolated From Clinical Samples In Pakistan, Sara Lomonaco, Matthew A. Crawford, Christine Lascols, Debra J. Fisher, Kevin Anderson, David R. Hodge, Segaran P. Pillai, Stephen A. Morse, Erum Khan, Molly A. Hughes, Marc W. Allard, Shashi K. Sharma

Department of Pathology and Laboratory Medicine

Infections in immunocompromised patients that are caused by extensively drug-resistant (XDR) Acinetobacter baumannii strains have been increasingly reported worldwide. In particular, carbapenem-resistant A. baumannii strains are a prominent cause of health care-associated infections. Here, we report draft genome assemblies for two clinical XDR A. baumannii isolates obtained from hospitalized patients in Pakistan.

Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander

Electronic Theses and Dissertations

Background: Tobacco smoking is the leading environmental risk factor for periodontal diseases. Delineation of the mechanisms underlying tobacco-induced or exacerbated periodontitis is hampered by the lack of an appropriate and reliable animal model. Hypothesis: We hypothesized that Porphyromonas-gingivalis-infected, cigarette smoke-exposed mice would represent reproducible models of acute (ligature model) and chronic (oral gavage model) tobacco-enhanced periodontitis that reflect multiple aspects of the disease noted in human smokers. Methods: In a chronic oral gavage disease model, Balb/c mice (6-8 weeks, 4 groups of n = 6 per group) were exposed to smoke produced by a Teague-10 smoking machine from 1R6F research …

Expression Of Her-2/Neu In Oral Squamous Cell Carcinoma, Sana Mirza, Naila Hadi, Shahid Pervez, Sultan Zeb Khan, Sameer A. Mokeem, Tariq Abduljabbar, Nawwaf Al-Hamoudi, Fahim Vohra

Department of Pathology and Laboratory Medicine

Background: HER-2/neu is a member of the human epidermal growth factor (HER) family of transmembrane tyrosine kinases, which is significantly associated with the pathogenesis of various cancer types. The aim was to evaluate the expression of HER-2/neu in oral squamous cell carcinoma (OSCC) as a potential biomarker to target antigens for specific immunotherapy in OSCC.
Methods: One hundred and forty histologically diagnosed OSCC cases were identified. Four to five-micrometer thick formalin-fixed, paraffin-embedded tumor sections were stained with Haematoxylin and Eosin (H and E). Histological grade was assessed according to WHO/Broders classification, while tumors were staged according to the American Joint …

Transcriptomic Responses To Coaggregation Between Oral Bacteria, V R Mutha Naresh

Student Works (2020-2029)

Cell-cell interactions between genetically distinct oral bacteria form macroscopic clumps known as coaggregates. These interactions, termed coaggregation contribute to the formation of highly structured multispecies communities in oral cavity, known as oral biofilms. Individual species also compete and collaborate with other neighboring species through metabolic interactions allowing growth of other species by coaggregation. This study involves the mixing of selected pairs of oral bacteria to form coaggregates and quantifying differential gene expression levels in each pair in comparison with mono-species coaggregation. The dual RNA-Seq approach made it possible to see how bacteria respond to one another leading to different metabolic …