Pathogenic Microbiology Commons^™

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 …

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 …

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 …

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, …

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 …

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 …

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 …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

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 …