Life Sciences Commons^™

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+) …

Testing Of Indazole Inhibitors Of Kasa, A Vital Enzyme Of M. Tuberculosis, Karissa Highlander

Student Research Submissions

Tuberculosis is a disease that affects the lungs caused by Mycobacterium tuberculosis (M. tuberculosis). Although drug treatment options exist, increased rates of antibiotic resistant strains have become more prevalent in recent years, driving a need for new treatment approaches. KasA, a β-ketoacyl synthase, has been found to synthesize parts of the cell wall and been identified as an attractive drug target. Previous medicinal chemistry research has been completed to synthesize six effective competitive inhibitors of KasA that would potentially block the enzyme from binding the substrate, preventing elongation of the backbone and creation of the mycolic fatty acids that …

Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.

Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Electronic Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and …

The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin

Arts & Sciences Electronic Theses and Dissertations

The mammalian immune system is composed of innate and adaptive compartments, which cooperate with each other to maintain homeostasis and protect the host from the invasion by a variety of pathogens. The tight control of immune responses is extremely important for all individuals. Here, we discovered that the transcription factor basic helix-loop-helix family, member e40 (Bhlhe40) is a critical protein that regulates the autoimmune ("against self") and anti-microbial ("against non-self") responses of myeloid cells and T lymphocytes. Multiple sclerosis (MS) is a human neuroinflammatory disease in the central nervous system with an autoimmune etiology. We have reported that Bhlhe40 positively …

Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer

Undergraduate Honors Thesis Collection

Tuberculosis (TB) is a highly infectious respiratory disease contracted through the inhalation of Mycobacterium tuberculosis. Serine hydrolases are abundant in M. tuberculosis and serve as a model for studying the inhibition of TB. Rv0045c is an example of such with little known regarding its biological function. Rv0045c was exposed to methanol, ethanol, isopropanol, or glycerol and the effects of varying concentration of these alcohols on the catalytic efficiency and thermal stability of the enzyme was determined. The thermal stability of Rv0045c was found to decrease with concentration of methanol, ethanol, or isopropanol. The opposite was true of the thermal stability …

Interactions Between Human Neutrophils And Mycobacterium Smegmatis : A Comparative General Analysis., Irina Miralda

College of Arts & Sciences Senior Honors Theses

Mycobacteria smegmatis is an abundant soil and water inhabitant with which humans are continuously in contact. Despite the fact that it is typically considered non-­‐pathogenic, a few rare cases of M. smegmatis-­‐caused infections have been reported and it has been shown that M. smegmatis is able to modulate inflammatory responses in macrophages. Neutrophils are the innate immune system’s first line of centralized defense against invading microbes, especially the frequently encountered M. smegmatis. However, very little information is known of the mechanism by which neutrophils eliminate environmental bacteria. In this study, the hypothesis that M. smegmatis regulates neutrophil functional responses, and …

The Hypericum Perforatum Herb As An Antimycobacterial Agent And Its Implications As An Additional Tuberculosis Medication, Trent W. Mortensen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

An immediate demand exists for new tuberculosis (TB) antibiotics due to the ever-increasing spread of drug-resistant strains. The drug-development process goes through four phases, the first (Phase 0) of which is to demonstrate and investigate drug effectiveness and toxicity. This research investigated the effectiveness of the Hypericum perforatum herb (commonly St. John's wort (SJW)) in its growth inhibition of mycobacteria and its viability effect on human lung cells.

Organic-solvent SJW extracts were effective at inhibiting every nonpathogenic genetically sequenced Mycobacterium isolate currently available (six isolates) in preliminary studies. Quantitative studies of five Mycobacterium isolates showed an order of concentration sensitivity …