Microbial Physiology Commons^™

Repurposing Cyclin-Dependent Kinase Inhibitors For The Discovery Of Novel Antiplasmodial Compounds, Ritam Bhowmik

Honors Undergraduate Theses

Malaria remains a major global health burden with over 282 million cases annually and rising resistance to artemisinin-based combination therapies. Plasmodium falciparum, the most lethal malaria parasite species in humans, relies on tightly regulated cell cycle progression during replication within red blood cells. Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell division and transcription, and several CDK-like enzymes in P. falciparum, including Pfmrk and PfPK6, are essential for parasite growth and structurally distinct from human kinases. This study evaluated whether commercially available human CDK inhibitors (CDKIs) targeting cancer pathways could be repurposed as novel antimalarial compounds. A library of …

Host, Microbiome, And Parasite: How Apicomplexan Microorganisms Interact With Gut Microbiota, Senia Bu, Andrew T. Ozga

Mako: NSU Undergraduate Student Journal

The gut microbiome, a complex ecosystem of microorganisms residing in the human gastrointestinal tract, plays a crucial role in maintaining overall health. It functions in immune system regulation, digestion, and protection against pathogens. Apicomplexan parasites, such as Toxoplasma gondii, Plasmodium spp., and Cryptosporidium spp., are major pathogens that can significantly disrupt the gut microbiota, leading to alterations in microbial composition and function. This review explores the bidirectional interactions between Apicomplexan parasites and the gut microbiome, focusing on how these parasites influence microbial diversity, immune responses, and host metabolism. It examines the mechanisms by which infection-induced inflammation, altered …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

The Physiological Significance Of Nitric Oxide Synthase In Staphylococci, Ryan M. Singh

Theses & Dissertations

Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO^•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO^•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity …

Characterizing The Regulation Of Candida Albicans Hyphal Morphogenesis In The Context Of Host Macrophages, Hannah Wilson

Dissertations and Theses (Open Access)

Candida albicans is a commensal fungus that resides on the skin, mucosal surfaces, and in the gut of an estimated 80% of individuals. Though generally harmless, C. albicans is capable of causing uncomfortable mucosal infections as well as deadly disseminated infections depending on the immune status of the host. Although antifungal therapeutics exist, the mortality rate associated with disseminated disease still lingers around 50%. Further, C. albicans is the fourth most common cause of all bloodstream infections and continues to present as a major clinical issue with less than satisfactory treatment options. For this reason, it is imperative to understand …

Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill

Dissertations and Theses (Open Access)

Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms …

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine

Theses and Dissertations (Comprehensive)

Riparian wetlands are unique habitats facilitating all forms of life. The riverbanks of these environments provide ideal conditions for bacteria, plants, and higher organisms. Of particular interest to this research was the variation in microbial community structure at high, intermediate and poor water quality impacted areas. Assessing the capabilities of plants to retain microbial pathogens was identified. Root systems and corresponding soil are ideal locations for bacterial deposition, resulting in attachment at these areas. Biofilm production in these regions is important for long-term establishment, leading to persistence and potential naturalization. Opportunistic pathogens originating from mammalian fecal matter are introduced into …

Regulation Of To Xin Synthesis By Clostridium Difficile, Charles Darkoh

Dissertations and Theses (Open Access)

Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect the bacterium, the toxins, or the toxin genes. These methods do not differentiate virulent C. difficile strains that produce active toxins from non-virulent strains that do not produce toxins or produce …

Campylobacter Ureolyticus: An Emerging Gastrointestinal Pathogen?, Susan Bullman, Daniel Corcoran, James O'Leary, Brigid Lucey, Deirdre Byrne, Roy D. Sleator

Department of Biological Sciences Publications

A total of 7194 faecal samples collected over a 1-year period from patients presenting with diarrhoea were screened for Campylobacter spp. using EntericBios, a multiplex-PCR system. Of 349 Campylobacter-positive samples, 23.8% were shown to be Campylobacter ureolyticus, using a combination of 16S rRNA gene analysis and highly specific primers targeting the HSP60 gene of this organism. This is, to the best of our knowledge, the first report of C. ureolyticus in the faeces of patients presenting with gastroenteritis and may suggest a role for this organism as an emerging enteric pathogen.

The Armadillo Repeat Protein Pf16 Is Essential For Flagellar Structure And Function In Plasmodium Male Gametes, Ursula Straschil, Arthur M. Talman, David J. P. Ferguson, Karen A. Bunting, Zhengyao Xu, Elizabeth Bailes, Robert E. Sinden, Anthony A. Holder, Elizabeth F. Smith

Dartmouth Scholarship

Malaria, caused by the apicomplexan parasite Plasmodium, threatens 40% of the world's population. Transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. The male gamete of Plasmodium parasite is the only developmental stage that possesses a flagellum. Very little is known about the identity or function of proteins in the parasite's flagellar biology. Here, we characterise a Plasmodium PF16 homologue using reverse genetics in the mouse malaria parasite Plasmodium berghei. PF16 is a conserved Armadillo-repeat protein that regulates flagellar structure and motility in organisms as diverse as green algae and mice. We show that …