Pathogenic Microbiology Commons^™

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 …

Tetrodotoxin, Fungal Pathogen Infection, And Bacterial Microbiome Associations Are Variable In The Skin Microecosystems Of Two Taricha Newt Species, Talon B. Jost

EWU Masters Thesis Collection

Chytridiomycosis is an amphibian disease linked to population declines and species extinctions, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). While chytridiomycosis can result in host death, some amphibians are less susceptible to severe infections through intrinsic factors including host-associated skin microbes aiding defense through resource competition and antifungal metabolite production. Amphibians can also release toxins in response to stress cues to defend against disease, parasitism, and predation. Tetrodotoxin (TTX) is a potent low molecular weight neurotoxin found in genus Taricha, and despite a previously observed negative relationship between differential levels of TTX concentration and Bd infection presence within a …

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 …

Genetic And Biochemical Analysis Of Novel Borrelia Burgdorferi Genes Bb0244 And Bb0246, Christian J. Ruiz-Rodriguez

Honors Undergraduate Theses

As the cause of the most common vector-borne disease in the US, Borrelia burgdorferi continues to affect an estimated hundreds of thousands of patients each year. The spirochete boasts one of the most complex genomes in comparison to all other prokaryotes as it is fragmented across up to 21 different replicons. Moreover, the functions of a majority of the encoded genes remain unknown. Gene of unknown function, bb0244, along with putative co-transcribed genes bb0245, and bb0246 are hypothesized to be involved in the vital functions of cell division and cell wall biogenesis. B. burgdorferi lacking bb0244 demonstrate a significant growth …

Invasion Of Superbugs: Cockroach-Driven Outbreak Of Multidrug-Resistant Enterobacter In An Icu, Jennifer Hanrahan, Nicholas Schouten, Steven H. Fyffe, Annette Jencson, Stephanie Stroever

Department of Medicine Faculty Publications

Objective: To describe factors in an outbreak of multidrug-resistant Enterobacter cloacae (MRE) in an intensive care unit (ICU) over a 20-month period including the likely contribution of cockroaches to the outbreak.

Design: This is a retrospective descriptive study.

Setting: ICU in an urban hospital.

Patients: All patients admitted to the ICU during the 20-month outbreak period were included in the study.

Interventions: Infection prevention interventions included contact isolation, hand hygiene, dedicated patient equipment, environmental cultures, and pest control.

Results: 25 patients were identified as being colonized or infected with MRE. Relatedness of the outbreak strain and strains found in cockroaches …

Salmonella Detection In Food Using A Hek-Htlr5 Reported Cell-Based Sensor, Esma Eser, Victoria A. Felton, Rishi Drolia, Arun K. Bhunia

Biological Sciences Faculty Publications

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount for supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, the pathogenic potential or health risk of the analyte at the time of consumption, the detection limit, and the sample-to-result. Mammalian cell-based assays analyze pathogens’ interaction with host cells and are responsive only to live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) …

Erwinia Amylovora Phage Therapy: Biocontrol Formulation, Receptor Identification, Resistance Mechanisms, Nassereldin Ibrahim

Theses and Dissertations (Comprehensive)

Fire blight is known as a disease of Rosaceae and it displays infection symptoms in about 200 species in 40 rosaceous genera. The most economically important crops that are affected by fire blight are apples and pears. Fire blight can cause severe outbreaks and a single fire blight outbreak can disrupt orchard production for years. The bacterium that causes this disease is indigenous in North America, and according to Statistics Canada, economic losses in apples and pears were valued at an estimated $4 million in 2005, which is approximately 5% of the total production. In addition, production costs can increase …