Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Pilz Domain-Containing Proteins Regulate Motility In Acinetobacter Baumannii, Gabriel Smith

Electronic Theses and Dissertations

Acinetobacter baumannii is an increasingly multidrug-resistant pathogen contributing to hospital-acquired infections, necessitating a greater understanding of how it interacts with its surroundings. Many bacteria utilize different methods of bacterial motility to move about and interact with these surroundings. A bacterial second messenger, cyclic diguanosine monophosphate (c-di-GMP), can regulate various motility factors that are potentially advantageous for survival in and adaptation to their environment. Concentrations of c-di-GMP are regulated by specific synthesizing and degrading enzymes. Controlled levels of c-di-GMP allow interaction between the c-di-GMP and its binding effectors that induce changes in bacterial phenotypes such as biofilm formation and motility. A …

Comprehensive Investigation Into The Molecular Mechanisms Driving The Emergence Of Emm4 Group A Streptococcus, Chioma Odo, Samuel A Shelburne, Anthony R. Flores, Steven J Norris, Anna Konovalova, Blake Hanson

Dissertations and Theses (Open Access)

Abstract

Comprehensive Investigation into the Molecular Mechanisms Driving the Emergence of emm4 Group A Streptococcus

Chioma Modeline Odo, M.S.

Advisory Professor: Samuel A. Shelburne, MD, Ph.D.

The major gram-positive bacterium group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it is well known to cause infections that occur in waves. GAS strains are grouped based on the composition of the N-terminal sequence of the M protein which is encoded by the emm gene. With the advent of large-scale whole genome sequencing, GAS clonal emergence events in emm1, emm3, and emm89 types have been identified …

The Impact Of Reactive Oxygen Species On Bactericidal Activity And Drug Resistance In Salmonella Typhimurium Upon Chlorine And Eugenol Exposure, Mohammed Aljuwayd

Graduate Theses and Dissertations

Salmonella Typhimurium (S.T) is a foodborne pathogenic bacterium which causes salmonellosis in human beings. Chicken is the most common source of S.T contamination. In chapter I, I discuss the growth of the poultry industry, the role chickens play as Salmonella reservoirs, the spread of drug-resistant strains caused by chicken husbandry and antibiotic use, and how eugenol can be used in poultry feed to decrease Salmonella infections and improve intestinal health. In chapter Ⅱ, I summarize the role of reactive oxygen species (ROS) in bactericidal activity. In chapter Ⅲ, I describe the killing mechanism of sodium hypochlorite (NaOCl) and identify the …

Candida Albicans Farnesol Synthesis And Secretion, Daniel J. Gutzmann

School of Biological Sciences: Dissertations, Theses, and Student Research

Candida albicans is a polymorphic fungus and opportunistic commensal found primarily in the gastrointestinal and skin of healthy individuals. Several barriers prevent C. albicans from causing disease including a healthy immune system and microbiome. When these barriers become comprised, C. albicans can transition to a pathogen and disseminate through the intestinal mucosa leading to life-threatening bloodstream and invasive infections with mortality rates of up to 64%. Morphogenic plasticity is key to this transition and impacts virulence, adaptation to different host environments, and evasion of host immune responses. One regulator of morphogenesis is farnesol. Farnesol is a secondary metabolite of …

Antibiotic-Induced Changes In Efflux Transporter Expression: A Key Factor In Pseudomonas Aeruginosa Biofilm Resistance, Zara Imtiaz, Avinash Chatoo, Will Wang, Weiqi Li, Paramita Basu

Touro College of Pharmacy (New York) Publications and Research

Listed by WHO as an antibiotic-resistant priority pathogen, Pseudomonas aeruginosa(P.A.) is a serious threat in nosocomial infections. Its high antibiotic resistance is attributed to major mechanisms that can be categorized into intrinsic, acquired, and adaptive resistance. This study tests the ability of three commonly used antibiotics to inhibit new biofilm formation and eradicate mature biofilm growth, as well as investigate changes in the expression levels of selected genes coding for multidrug efflux pumps in P.A. planktonic cells and biofilms before and after treatment with antibiotics to provide a conceptual estimate of the activity of the efflux transporters that work to …

Impact Of Salmonella Enterica On Plant Physiology And Immunity, Sara Qader

Poster Presentations

Salmonella can colonize plant tissue effectively. Understanding the molecular mechanisms underlying Salmonella’s interactions with plants is essential for developing effective strategies to reduce its impact on human health and agriculture. Effector proteins, known for their role in modulating host-pathogen interactions, have been implicated in the virulence and pathogenicity of Salmonella. However, their specific functions and contributions to Salmonella’s interactions with plants remain largely unknown. Here, we aim to investigate the functions of Salmonella effector proteins during the colonization of plants.

Characterization Of Ato Family Transporters In The Fungal Pathogen Cryptococcus Neoformans, Will Betsill

All Theses

Fungal pathogens are a significant threat to public health as they are becoming increasingly common and more resistant to treatment. Cryptococcus neoformans contributes greatly to this threat annually by causing an estimated 278,000 cases of cryptococcal meningitis resulting in approximately 181,000 deaths globally according to the CDC. C. neoformans is ubiquitous across most of the globe and can be found in such places as in trees or soil. Exposure to this fungus is especially dangerous to individuals who are immunocompromised or immunosuppressed. In these cases, inhalation of spores can lead to infection in the lungs. Once in the lungs, C. …

Analysis Of Antibiotic Sensitivity Patterns In Pasteurellaceae Family Isolates: A Microbial And Molecular Investigation, Jillian Barron

Honors Scholar Theses

Bacteria in the Pasteurellaceae family are known to cause disease in both human and animal species. Like all species of bacteria, the pathogens in the Pasteurellaceae family evolve and acquire antimicrobial-resistant traits. Antimicrobial resistance of bacteria is a significant public health concern, as treatment of resistant pathogens becomes more difficult, if not impossible, with current medical capabilities. In this project, phenotypic and genotypic analyses were performed on Pasteurellaceae family isolates sourced from the Connecticut Veterinary Medical Diagnostic Laboratory. Phenotypic antibiotic sensitivity patterns of each isolate were assessed against a panel of antibiotics through a Kirby-Bauer disk diffusion test. Disk diffusion …

Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick

Theses/Capstones/Creative Projects

In the context of rising multidrug resistance in biofilm-forming pathogens like Pseudomonas aeruginosa, this study investigates the role of the understudied transcription factor PA5189 in antibiotic resistance and biofilm formation. PA5189 deletion and overexpression mutants were created in a parent P. aeruginosa strain using pEX18Tc-based recombinant suicide vectors, with genotypic verification of putative triparental conjugants achieved through restriction digestion and PCR. The study revealed that PA5189 overexpression significantly increases resistance to commonly used broad spectrum antibiotics such as ciprofloxacin and imipenem. Additionally, differential expression of PA5189 was found to notably affect biofilm formation, with variations contingent on the nutrient …

Determining The Antimicrobial Activity And Permeabilizing Effects Of Polyunsaturated Fatty Acids And Piscidins On Vibrio Parahaemolyticus And Vibrio Vulnificus, Christina Harris

Honors Theses

Antimicrobial peptides (AMPs) are found in all organisms and have gained attention for their effectiveness against a variety of pathogens. Piscidins are AMPs that were discovered in mast cells of vertebrates, mostly within marine animals, and are an important part of the innate immune system due to their potent antimicrobial properties. Piscidin 1 (P1) and piscidin 3 (P3) are found within sea bass and have different antimicrobial activities. P1 exhibits strong membrane disruptive properties, while P3 goes through the membrane to the targeted DNA. These piscidins can experience metalation with copper (Cu2+) which enhances their antimicrobial activity in vitro (P1-Cu2+ …

Exploring Novel Nutrient Acquisition Mechanisms For Maintaining Energy Metabolism In Toxoplasma Gondii, Melanie Key

All Dissertations

Toxoplasma gondii is an infectious intracellular parasite that establishes infection within various mammalian hosts, including humans. Toxoplasma infects approximately one-third of the global population, making it an impactful pathogen of study. T. gondii is the causative agent of toxoplasmosis, an opportunistic infection that causes severe illness or fatality in immunocompromised individuals or pregnant women. The parasite possesses a very effective invasion strategy, allowing it to cross different tissue types to disseminate infection across the placental and blood-brain barrier. Although there are a few treatments for acute toxoplasmosis, these drugs can produce adverse side effects. These options are not effective against …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Investigating Vital Neutrophil Extracellular Trap Pathogen Response In Neutropenic Individuals, Ryan Illig

Thinking Matters Symposium

Neutrophils, also called polymorphonuclear leukocytes (PMNs), constitute the majority of innate immune cells. These cells possess a complex arsenal of functions that allow them to detect and eliminate a broad spectrum of pathogens. Neutropenia is characterized by decreased levels of neutrophils in the bloodstream, typically falling below the normal range. Moderate to severe neutropenia can increase the risk of pathogenic infections and without treatment can be life-threatening. Although the concentration of neutrophils in neutropenic individuals is decreased, upon activation, neutrophils still release neutrophil extracellular traps (NETs). NETs are pivotal in combating a spectrum of pathogens through their non-selective nature. Overreactive …

Mechanistic Insights On Positive Regulation Of The Pyrin Inflammasome In Macrophages, Haleema Sadia Malik

Dartmouth College Ph.D Dissertations

The mammalian innate immune defense employs sophisticated mechanisms, such as effector triggered immunity (ETI), to discern between pathogenic and non-pathogenic bacteria and initiate a protective response. ETI is involved in immune detection of virulent activities of bacterial effector proteins in the host cytosol. Inflammasome sensors, such as pyrin, detect cellular infection or stress as part of ETI, leading to the assembly of multiprotein complexes, caspase-1 activation and proinflammatory cytokine release. Pyrin uniquely initiates inflammatory responses against RhoA-inactivating bacterial toxins and effectors such as Yersinia's YopE and YopT, and C. difficile’s toxins TcdA/B. Understanding pyrin regulation is crucial due to its …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

The Influence Of Cards Toxin In Abetting The Virulence Of Mycoplasma Pneumoniae, Layla Abdulbaki

Posters - 2024

Mycoplasma pneumonia is a human bacterial pathogen known to induce chronic upper and lower respiratory infections. This bacterium commonly causes acute, chronic infections, such as atypical pneumonia, and spreads through droplet transmission (> 5 microns). M. pneumoniae damages cells by attacking the epithelium of the respiratory tract, resulting in epithelium shedding. Infection of the airway tract by M. pneumoniae will usually express itself in people with chronic symptoms such as coughing, dyspnea, diarrhea, and epiphora. With this being said, this bacterium is ambit, meaning that it is versatile in who it affects (children to adults), how it manifests (pneumonia, tracheobronchitis, …

Shigella Flexneri Diguanylate Cyclases Regulate Pathogenesis, Ruchi Ojha

Dissertations

The intracellular human pathogen Shigella invades the colonic epithelium to cause disease. Prior to colon invasion, this bacterium navigates through different environments within the human body, including acidic conditions in the stomach and the small intestine which contains antimicrobial molecules including bile acids. To adapt to changing environments, Shigella uses the bacterial second messenger c-di-GMP signaling system. C-di-GMP is synthesized by diguanylate cyclases (DGCs) encoding GGDEF domains. Shigella encodes 10 DGCs in its genome, but 6 of these genes have acquired mutations that presumably inactivated the c-di-GMP synthesis activity of these enzymes. In this study, we first expressed VCA0956, a …

Adherent-Invasive Escherichia Coli (Aiec) Promotes Mild Colitis In The C57bl/6 Il-10 Ko Mouse Model Of Crohn's Disease, Sarah Sm Zaw

Senior Theses

Crohn's disease (CD) is a chronic inflammatory bowel disease. Interleukin-10 knockout (IL-10 KO) mice are crucial in CD research. Adherent-invasive Escherichia coli (AIEC) is a subgroup of E. coli. In one study, IL-10 KO mice colonized with AIEC developed colitis in the distal colon compared to wild-type (WT) mice. I investigated how AIEC NC101 WT affects colitis severity in IL-10 KO mice of the C57BL/6 genetic background. Similar results in both genotypes would enhance mouse strain accessibility. Germ-free C57BL6 IL-10 KO mice were divided into groups: colonized with AIEC NC101 for 12, 15, or 18 weeks, or kept germ-free. Histopathological …

Exploring The Role Of Calcineurin In Filamentation Across Inducing Conditions In The Fungal Pathogen Candida Albicans, Patricia Harte-Maxwell, Jill R. Blankenship

UNO Student Research and Creative Activity Fair

Candida albicans is an opportunistic human pathogenic fungus affecting millions of people globally; high mortality rates are possible in systemic infection. Filamentation or a filamentous growth pattern is a primary virulence mechanism of C. albicans underlying other virulent behaviour....

Adaptive Evolution Of Surface Proteins In Microbial Pathogens: Lyme Disease Pathogens (Borreliella Sp.) And Human Immunodeficiency Virus Type 1 (Hiv-1), Li Li

Dissertations, Theses, and Capstone Projects

Cell and virion surface proteins are key to the survival and adaptation of microbial pathogens by enabling them to evade host immune responses and to persist in diverse environments. Pathogens respond to host immune pressures with genetic changes in surface proteins through mechanisms including point mutations, recombination, gene duplication and loss, and lateral gene transfer, resulting in novel antigenic variants and antigenic diversity. This continuous adaptation helps pathogens evade host immunity, leading to chronic infections and recurrent disease outbreaks. Understanding these mechanisms is vital for developing effective strategies to combat infectious diseases.

This dissertation comprises three chapters exploring the adaptive …

Dpr-Mediated H2o2 Resistance Contributes To Streptococci Survival In A Cystic Fibrosis Airway Model System, Rendi R. Rogers

Dartmouth College Master’s Theses

The cystic fibrosis (CF) lung environment is conducive to the colonization of bacteria as polymicrobial biofilms, which are associated with poor clinical outcomes for persons with CF (pwCF). Streptococcus spp. is highly prevalent in the CF airway, but its role in the CF lung microbiome is poorly understood. Some studies have shown Streptococcus spp. to be associated with better clinical outcomes for pwCF, while others show that high abundance of Streptococcus spp. is correlated with exacerbations. Our lab previously reported a polymicrobial culture system consisting of four CF-relevant pathogens that can be used to study microbial behavior in a more …

Managing Stress: A Study Of Stress Response Mechanisms In Mycobacteria, Augusto C. Hunt Serracin

Biology Dissertations - Archive

Mycobacteria encompass many pathogenic species known to cause severe disease in humans. A well-known example is Mycobacterium tuberculosis (Mtb), the causative agent of the lung disease tuberculosis, which kills millions of humans worldwide yearly. Pathogenic mycobacteria like Mtb are challenging to treat because of their innate ability to adapt to environmental stress. Their unique cell physiology and conserved stress responses allow them to combat biological insults, regulate growth, and regulate genes involved in stress; all these responses increase tolerance to antibiotics. The current therapies to treat mycobacterial infections are lengthy and, at times, unsuccessful, partly due to antibiotic tolerance. A …

Reiq-Mediated Alarmone Signalling Regulates Growth, Stress-Induced Biofilm Formation And Spore Accumulation In Clostridioides Difficile, Areej Malik, Adenrele Oludiran, Asia Poudel, Orlando Berumen Alvarez, Charles Woodward, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signalling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in Clostridioides difficile, a biofilm- and spore-forming pathogen that causes resilient, highly recurrent C. difficile infections. The role of the SR in other processes and the effectors by which it regulates C. difficile physiology are unknown. C. difficile RelQ is a clostridial alarmone synthetase. Deletion of relQ dysregulates C. difficile growth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors and drastically reduces biofilm formation. While wild-type C. difficile displays increased biofilm …

Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The obligate anaerobe Clostridioides difficile encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024, https://doi.org/10.1128/mbio.01591-24). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP …

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Temporal Distribution Of Potential Waterborne Pathogens In Sequiota Spring, William J. Durstock

Graduate Theses/Dissertations

Waterborne pathogens from human fecal matter pose a significant health risk in karst environments, where domestic wastewater can easily be transferred to the shallow groundwater system via old, leaky septic tanks and damaged sewer lines. This study monitored fecal indicator bacteria (FIB) and potential pathogens in Sequiota Spring located in the karst region of southwest Missouri, using Microbial Source Tracking (MST) and Illumina DNA sequencing of bacterial 16S rRNA genes. MST identified high levels of human fecal indicator bacteria (HFIB) (up to 110,000 cells/L) in July 2020. By June 2022, HFIB levels had dropped significantly (55-fold reduction) after the City …

Investigating Birds As Dispersal Vectors Of Litylenchus Crenatae Subsp. Mccannii (Anguinidae), The Nematode Associated With Beech Leaf Disease, Spencer Rock Parkinson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Beech leaf disease (BLD) is an emerging forest pathogen primarily affecting American beech (Fagus grandifolia, Ehrh.) in North America and has been attributed to tree mortality of sapling sized trees within five to seven years of infection. Symptoms typically occur in regenerating American beech thickets sprouting from roots of trees killed by beech bark disease. Scientists first observed BLD in Ohio in 2012 and currently has spread to 15 states in the USA and one Canadian province. The nematode Litylenchus crenatae subsp. mccannii (Lcm) is highly associated with BLD symptoms, interveinal chlorosis and defoliation of leaves, and is currently …

Characterization Of Host Cell Specific Interactions During Spotted Fever Group Rickettsiae Infection, Emerson Towey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Vector-borne diseases have been increasing over the past few years due to changes in climate and disturbances in the vectors’ natural environment. To mitigate the risks of these diseases, it is necessary to understand pathogen biology and how it interacts with a host to cause disease. Here we focus our attention on the tick-borne pathogen, Rickettsia rickettsii. R. rickettsii is a member of the spotted fever group (SFG) Rickettsiae and is the etiological agent of Rocky Mountain spotted fever (RMSF), a fatal human disease that is lacking an effective vaccine. Members of the bacterial genus Rickettsia are obligate intracellular endoparasites …