.jpg) Microbiology and Immunology Graduate Program
B.S., Biology, Kutztown University
Email: kelley.r.healey@drexel.edu
Advisor: Thomas Edlind, Ph.D
Thesis Research Summary:
One area of research in our lab involves studying the mechanisms of resistance developed by fungi towards various antifungal drugs. My current project involves the echinocandins, the newest group of antifungals. These drugs are highly active against the opportunistic fungal pathogens Candida albicans and C. glabrata and are assumed to target fungal cell walls through inhibition of β-1,3-glucan synthase. Because C. glabrata is intrinsically less susceptible to the commonly used azole antifungals, the echinocandins, including caspofungin and micafungin, have been elevated to first line agents in the treatment of C. glabrata invasive infections. Although rare, reports of clinical resistance are increasing with increasing use and are strictly associated with mutations in β-1,3-glucan synthase genes FKS1 and FKS2.
We have generated C. glabrata mutants that exhibit a differential echinocandin susceptibility phenotype. In other words, they exhibit low-level resistance to one echinocandin and hypersensitivity to another. Through sequencing, gene disruption, and lipid analysis, we have found that these mutants lack any Fks alterations and arise from mutations within the sphingolipid biosynthesis pathway that lead to the accumulation of specific pathway intermediates. These studies suggest the possibility that sphingolipid pathway inhibitors could be used to enhance activity of specific echinocandins. In the future, we would like to study the lipid environment surrounding β-1,3-glucan synthase and will continue to attempt to increase antifungal effectiveness and further understand the mechanisms of resistance that are associated with these drugs.
Outside of lab, I enjoy attending Phillies games and happy hours, attempting to still play in a few competitive field hockey games, and swimming in the ocean back home in NJ.
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