Genetic characterization of C. auris adhesion

项目总结/文摘

Project Summary/Abstract Adherence is a key factor determining whether organisms can persist and transmit on abiotic surfaces. This attachment also is the first step in the formation of biofilms, which are linked with both persistence and antifungal drug resistance. Candida auris, an emerging fungal pathogen, can cause outbreaks in hospital settings. This is likely linked with its ability to adhere and persist on surfaces, as strains with low adhesive capacity are less likely to cause hospital outbreaks. However, the cell biology and genetic circuitry underlying the ability of C. auris to attach to surfaces are not known. Our long-term goal is to identify how C. auris senses and responds to abiotic surfaces to allow for robust attachment, and thus persistence, biofilm formation, and transmission. This application details experiments to address a fundamentally important gap in our knowledge of the components involved in the adherence of C. auris. We propose that C. auris responds to environmental cues by increasing adherence to surfaces, and that this adherence is a key virulence trait. We recently developed genetic tools for interrogating this organism, giving us unprecedented power to analyze the genes required for C. auris outbreaks. In Aim 1, we will use both forward and reverse genetic approaches to investigate the role of adhesins and other components in the ability of C. auris to attach to surfaces. In Aim 2, we will test the hypothesis that C. auris responds to specific environmental stresses by transcriptionally regulating adhesion effectors. We will use transcriptional profiling experiments and candidate promoter analyses to dissect out regulatory circuitry controlling attachment. Together, these studies will advance new concepts for how C. auris can regulate adherence.