Discovering the transcriptional network controlling flocculation in Candida albicans
Gabriel Viramontes, Craig. L. Ennis, & Clarissa J. Nobile
Candida albicans is a commensal of the human microbiota and is also the most common human fungal pathogen. Changes to the host immune system, pH, and resident microbiota can lead to C. albicans overgrowth, causing life-threatening disseminated infections. Caspofungin acetate is frequently used to treat invasive Candida infections in the clinic. Interestingly, C. albicans yeast cells flocculate, i.e. they tightly adhere to one another, in response to caspofungin treatment. These adhered cells form structures akin to biofilms, surface attached microbial communities surrounded by extracellular matrices. We identified nine transcription factors (TFs) controlling caspofungin-induced flocculation in C. albicans, several of which are known to also regulate biofilm development. We hypothesize that genes regulated by these TFs may be functionally relevant to both flocculation and biofilm development. We compared our caspofungin treated and non-treated wildtype C. albicans cells using RNA sequencing and identified twenty-five highly upregulated genes that we hypothesize are involved in 1) cellular responses to caspofungin 2) flocculation, and/or 3) biofilm development. Using CRISPR/Cas9 genome editing, we will delete each of these twenty-five genes that we will test for alterations in flocculation and biofilm development. In addition, using Gene Ontology analysis, we will identify which categories of biological functions our genes of interest are most associated with. Together, this work will illuminate the regulatory mechanisms and downstream effectors contributing to flocculation and may identify novel mediators of biofilm development and caspofungin resistance or tolerance.
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