Medical Microbiology Commons^™

Interplay Of Antibody Responses To Closely Related Viruses And Autoimmunity, Chun-Yang Lin

Theses and Dissertations (ETD)

Antibodies produced by B cells are crucial for eliminating infectious pathogens and preventing secondary infection. However, antibodies may also bind to self-antigens and contribute to autoimmune disease. While pathogen infections have been associated with development of autoimmune diseases, the precise contributions of viral infections to autoimmunity remain elusive. The presence of autoreactive antibodies is associated with an increased risk of developing autoimmune disease. Thus, analyzing the impact of viral infection and vaccination on the development of autoreactive antibodies will provide essential insight into mechanisms that contribute to autoimmune disease.

Examining How Non-Antifungal Medications Impact Host-Fungal Interactions, Parker Ryan Reitler

Theses and Dissertations (ETD)

Invasive fungal infections (IFIs) are estimated to kill 1.5 million people each year with mortality rates remaining high (around 30-70%), despite the availability of three major classes of antifungal drugs. Furthermore, millions more suffer debilitating infections of the mucosal membranes or destructive subcutaneous mycoses. One of the most common IFIs is invasive candidiasis, mostly commonly caused by Candida albicans infections, with mortality rates of approximately 30%. In addition, the population of susceptible individuals and the incidences of both mucosal and systemic mycoses continue to rise due to the widespread use of broad-spectrum antibacterial agents, cancer chemotherapies, and the immune suppressive …

Ftsk Regulates The Assembly Of The Division Machinery In The Ftsz-Less Chlamydia Trachomatis, Mckenna Katherine Harpring

Theses and Dissertations (ETD)

In evolving to obligate intracellular dependence, Chlamydia trachomatis serovar L2 (Ct), has eliminated several gene products essential for cell division in most other bacteria, including FtsZ, the central coordinator of divisome assembly. In the absence of FtsZ, we show that divisome assembly in Ct is initiated by FtsK, a chromosomal translocase. Chlamydial FtsK forms discrete foci at the septum and at the base of the progenitor mother cell, and our data indicate that FtsK foci at the base of the mother cell mark the location of nascent divisome complexes that form at the site where a daughter cell will emerge …

Synergistic Effects Of Antimicrobial Components Of The Human-Derived Composite Amnion-Chorion Membrane On Bacterial Growth

Faculty, Staff and Student Publications

Introduction: The human-derived amnion-chorion membrane (ACM) has endogenous antimicrobial properties, which are important for preventing the colonization and survival of oral bacteria on exposed membranes. This project aimed to decipher the underlying mechanism by identifying the components of ACM that confer antibacterial properties. In addition, the antimicrobial efficacy of these identified components on oral bacteria was assessed.

Methods: Four antimicrobial proteins, histone H2A/H2B, cathelicidin LL-37, lactoferrin, and lysozyme, were identified via mass spectrometry in ACM. These proteins were then assessed for their efficacy in killing Streptococcus gordonii Challis. Log-phased bacterial cells were cultured with the commercially available proteins that were …

Development Of 3d Cell Culture Model For Graves’ Ophthalmopathy, Rajit Chompoowong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Orbital tissue fibrosis and remodeling contribute to the development of exophthalmos, a hallmark symptom of Graves’ ophthalmopathy (GO). The central pathogenesis to this process are orbital fibroblasts (GOF), which express autoantigen, thyroid-stimulating hormone receptor (TSHR). However, there are limitations in preclinical models for studying the pathogenesis and drug discovery of GO, which poses challenges for developing effective treatment options. This study aimed to identify markers of GOF, explore epigenetic alteration, and develop a scaffold-free 3D cell culture model for GO. The novel results from immunohistochemical analysis showed that vimentin was uniquely expressed in GO but absent in control samples. Additionally, …

Effects Of Stat3 Variant On Stat1 And Stat5b In Fibroblasts From Mice With Stat3 Gain-Of-Function Variant, Natthakan Thareram

Chulalongkorn University Theses and Dissertations (Chula ETD)

STAT mutations cause immune system dysfunction and many diseases, such as autoimmune cytopenias, lymphoproliferative disorders, susceptibility to infections, endocrinopathies, and growth defects. However, the molecular activity of these proteins remains unclear. Here, we investigated the phosphorylation, nuclear translocation, and gene expression levels of Stat1, Stat3, and Stat5b, as well as downstream target genes of these proteins, using mouse fibroblasts with Stat3 wild type and Stat3 L387R gain-of-function (GOF) variant edited by CRISPR-Cas9 technique as a model. In fibroblasts of Stat3 L387R GOF animals, the expression of downstream target genes of STAT1, Cxcl10 and Irf7 were significantly decreased compared with Stat3 …

Insights Into The Assembly And Regulation Of The Bacterial Divisome, Todd A Cameron, William Margolin

Faculty, Staff and Student Publications

The ability to split one cell into two is fundamental to all life, and many bacteria can accomplish this feat several times per hour with high accuracy. Most bacteria call on an ancient homologue of tubulin, called FtsZ, to localize and organize the cell division machinery, the divisome, into a ring-like structure at the cell midpoint. The divisome includes numerous other proteins, often including an actin homologue (FtsA), that interact with each other at the cytoplasmic membrane. Once assembled, the protein complexes that comprise the dynamic divisome coordinate membrane constriction with synthesis of a division septum, but only after overcoming …

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Marie-Françoise Doursout, Marcos I Restrepo, Pooja Shivshankar

Faculty, Staff and Student Publications

Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, of which idiopathic pulmonary fibrosis (IPF) is the most devastating pathologic form. Idiopathic pulmonary fibrosis pathogenesis leads to loss of lung function and eventual death in 50% of patients, making it the leading cause of ILD-associated mortality worldwide. Persistent and subclinical microbial infections are implicated in the acute exacerbation of chronic lung diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, and microbial infections as major causes for the progression and exacerbation of IPF, the role of persistent microbial infections in the pathogenesis of IPF …

A Bibliometric Analysis Of Literatures On Uterine Leiomyosarcoma In The Last 20 Years, Dingwen Huang, Xiaochun Chen, Zhiying Yu

Faculty, Staff and Student Publications

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS.

Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed …

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …

The Potential For Development Of Clinically Relevant Microbial Resistance To Rifaximin-Α: A Narrative Review

Faculty, Staff and Student Publications

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Bacterial Outer Membrane Vesicles Provide An Alternative Pathway For Trafficking Of Escherichia Coli O157 Type Iii Secreted Effectors To Epithelial Cells, Anne Marie Krachler

Faculty, Staff and Student Publications

Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators …

Interlaboratory Comparison Of Pseudomonas Aeruginosa Phage Susceptibility Testing, Krupa Parmar, Lauren Komarow, Damon W Ellison, Andrey A Filippov, Mikeljon P Nikolich, Martin Lee, Priyesh Agrawal, Pranita D Tamma, Maria Souli, Scott R Evans, Kerryl E Greenwood-Quaintance, Scott A Cunningham, Robin Patel, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay. Four Pseudomonas aeruginosa phages: PaWRA01ø11 (EPa11), PaWRA01ø39 (EPa39), PaWRA02ø83 (EPa83), PaWRA02ø87 (EPa87), and a cocktail of all four phages were tested against 145 P. aeruginosa isolates. Comparisons were made within measurements at the two sites performing the liquid assay and between these …

Recombination-Mediated Dissemination Of Methicillin-Resistant S Aureus Clonal Complex 1 In The Egyptian Health Care Settings, Salma W Elsayed, Reem A Elghaish, Eman Badr, Shaimaa F Mouftah, Nehal A Saif, Ahmed H Shata, Samuel K Sheppard, Mohamed Elhadidy

Faculty, Staff and Student Publications

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly evolving pathogen that is frequently associated with outbreaks and sustained epidemics. This study investigated the population structure, resistome, virulome, and the correlation between antimicrobial resistance determinants with phenotypic resistance profiles of 36 representative hospital-acquired MRSA isolates recovered from hospital settings in Egypt.

Results: The community-acquired MRSA lineage, clonal complex 1 (CC1) was the most frequently detected clone, followed by three other globally disseminated clones, CC121, CC8, and CC22. Most isolates carried SCCmec type V and more than half of isolates demonstrated multi-drug resistant phenotypes. Resistance to linezolid, a last resort antibiotic for …

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …

Quantifying Non-Muscle Myosin 2 Filament Dynamics, Melissa Ann Quintanilla

Dissertations

Non-muscle myosin 2 is a motor protein that, when assembled into filaments, works on the actin cytoskeleton to produce contractile forces within cells. This type of myosin dynamically assembles within cells to exert forces necessary for a wide variety of functions including cell division, migration, and multicellular movement. The ability to dynamically assemble contractile networks, and the ability to control the assembly and placement of these myosin filaments in both space and time, is therefore required throughout cell physiology. We used a suite of dynamic, quantitative imaging approaches to identify deterministic factors that drive myosin filament appearance and amplification as …

Illuminating Type Iv Secretion-Mediated Dna Trafficking Through Long Filaments

Faculty, Staff and Student Publications

No abstract provided.

Benzodioxane-Benzamides As Ftsz Inhibitors: Effects Of Linker's Functionalization On Gram-Positive Antimicrobial Activity, Carlo Zanotto, Ermanno Valoti

Faculty, Staff and Student Publications

FtsZ is an essential bacterial protein abundantly studied as a novel and promising target for antimicrobials. FtsZ is highly conserved among bacteria and mycobacteria, and it is crucial for the correct outcome of the cell division process, as it is responsible for the division of the parent bacterial cell into two daughter cells. In recent years, the benzodioxane-benzamide class has emerged as very promising and capable of targeting both Gram-positive and Gram-negative FtsZs. In this study, we explored the effect of including a substituent on the ethylenic linker between the two main moieties on the antimicrobial activity and pharmacokinetic properties. …

Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana

School of Graduate Studies Faculty Publications

Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques. Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 …