Date Approved
5-2014
Document Type
Thesis
Degree Name
Master of Science in Molecular Pathology and Immunology
Department
Molecular Biology
College
Graduate School of Biomedical Sciences
First Advisor
Salvatore Caradonna, PhD
Committee Member 1
Scott Gygax, PhD
Committee Member 2
Grant Gallagher, PhD
Subject(s)
Candida; Vulvovaginal Candidiasis; Vaginal Yeast Infection; Antifungal Agents; Antifungal Drug Resistance; Fluconazole
Disciplines
Cell Biology | Female Urogenital Diseases and Pregnancy Complications | Fungi | Heterocyclic Compounds | Medicine and Health Sciences | Molecular Biology | Molecular Genetics
Abstract
Vulvovaginal candidiasis is the most common fungal infection of the female urogenital tract, commonly caused by Candida albicans and C. glabrata. However, treatment can be difficult when caused by non-albicans strains due to resistance to the oral antifungal drug fluconazole. The mechanism through which strains of Candida, particularly C. glabrata, develop resistance to different antifungal classes has not been completely characterized. The ergosterol biosynthesis pathway, an important component of the cell membrane, is the major target of antifungals such as fluconazole, an inhibitor of the ERG 11 gene. Current research shows that an upregulation of specific genes in C. glabrata known to regulate (PDRl) and encode efflux pumps (CDRl, PDHl, and SNQ2) is a common method of fluconazole resistance. Understanding the mechanism of resistance and antifungal susceptibility profiles is important for successful therapy. Thus, the hypotheses of this research are that fluconazole can be used to predict the susceptibilities of isolates to other antifungals, and that efflux pump regulation acts the same way in all fluconazole isolates. To test these hypotheses, a library of clinical C. glabrata isolates was collected and characterized by antifungal susceptibility testing against various antifungals in order to compare and contrast with fluconazole susceptibility profiles. It was determined that fluconazole cannot be used to predict the susceptibility to other antifungals. Additionally, through PCR testing, it was determined that the upregulation of genes encoding efflux pumps does not behave in similar fashion across a wide array of non-susceptible isolates.
Recommended Citation
Hardaker, David, "The Development of a Comprehensive Antifungal Susceptibility Testing Assay for Vulvovaginal Candidiasis Therapy" (2014). Graduate School of Biomedical Sciences Theses and Dissertations. 68.
https://rdw.rowan.edu/gsbs_etd/68
Included in
Cell Biology Commons, Female Urogenital Diseases and Pregnancy Complications Commons, Fungi Commons, Heterocyclic Compounds Commons, Molecular Biology Commons, Molecular Genetics Commons
