Investigation of Novel Virulence Mechanisms In Candida Albicans

<p><em>Candida albicans </em>is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, <em>C. albicans </em>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 <em>C. albicans </em>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 neutrophils. Due to the few options of current antifungal drugs and rising rates of drug resistance, building our understanding of <em>C. albicans </em>pathogenicity is key to determining how this fungal species interacts with the cells most responsible for its recognition and clearance. Alternative carbon utilization has been shown throughout the years to be an essential requirement for <em>C. albicans </em>in host-pathogen interaction models. This idea is expanded in this thesis by the discovery of additional genetic contributors to pH neutralization, a process that is critical for survival after phagocytosis by macrophages, and that the utilization of amino acids and <em>N</em>-acetylglucosamine are genetically distinct pathways. Furthermore, there are uncharacterized genes that <em>C. albicans </em>upregulates upon contact with mammalian macrophages and these genes are involved in well-described virulence mechanisms. The majority of these newly annotated genes were completely unstudied at the outset of this study and I have described the first <em>in vitro </em>and <em>in vivo </em>phenotypic assessments of several of these. Mia1, a microadhesin that has virulence-associated phenotypes is characterized for the first time in this study. We hypothesize that this small adhesin may serve a broader role of coordinating other surface adhesins based on the data presented. Taken together, this work describes new contributors to pathways known to affect the interactions of <em>C. albicans </em>with the host, which may inform future guided efforts to therapeutically target the virulence of <em>C. albicans</em>.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2018

Authors dc:creator

• Tafoya Vesely, Elisa Marie
• <p>https://orcid.org/0000-0003-4745-9276</p>

Contributors dc:contributor

• Michael Lorenz, Ph.D.
• Theresa Koehler, Ph.D.
• Kevin Morano, Ph.D.

• Fungal pathogenesis
• Candida albicans
• pH neutralization
• small proteins
• Bacterial Infections and Mycoses
• Pathogenic Microbiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/916

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1964