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Host Mediated Mechanisms Of Fungal Cell Spread In A Transparent Zebrafish Infection Model, Allison Scherer Dec 2018

Host Mediated Mechanisms Of Fungal Cell Spread In A Transparent Zebrafish Infection Model, Allison Scherer

Electronic Theses and Dissertations

Innate immunity has developed elegant processes for the detection and clearance of invasive fungal pathogens. Disseminated candidiasis is of significant concern for those with suppressed immune systems or indwelling medical equipment, and mortality in these groups approaches 70%. Poor patient outcomes have spurred the need to understand how this non-motile pathogen spreads in the host. Technical limitations have previously hindered our ability to visualize the role of innate immunity and host tissue barriers in the spread of C. albicans in vivo. Using the zebrafish model to overcome these limitations, we have examined three potential host-mediated mechanisms of dissemination: movement …


Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely Dec 2018

Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely

Dissertations & Theses (Open Access)

Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …


Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez May 2018

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

MSU Graduate Theses

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …


Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best May 2018

Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best

Electronic Theses and Dissertations

Legionella pneumophila is an environment organism that parasitizes a wide range of protozoa. Growth within the environmental host primes L. pneumophila for infection of human alveolar macrophages when contaminated aerosols are inhaled. Intracellular replication within either host requires the establishment a replicative niche, known as the Legionella-containing vacuole (LCV). Biogenesis of the LCV depends on the type IVb translocation system, the Dot/Icm, to translocation >320 effectors into the host cytosol. Effectors are responsible for preventing lysosome fusion to the LCV, recruitment of ER-derived vesicles to the LCV, and modulation of a plethora of host processes to promote the intracellular …


Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook Jan 2018

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …