Annual Report 2016-2017: Student Life & Development

Student Life and Development (SLD) professionals at Winona State University (WSU) deliver programs, services, and activities that support students\u27 academic achievement, social development, and well-being in the timely pursuit of their educational goals. The 2016-2017 SLD Annual Report provides information from the following departments: Admissions, Community Engagement, Conduct & Citizenship, Counseling & Wellness, Dean of Students, Fitness & Wellness, Health & Wellness Services, Housing & Residence Life, Inclusion & Diversity Office, Integrative Wellness, Intramurals, Student Activities & Leadership, TRIO Student Support Services, the Student Union, the Warrior Hub, and the Warrior Success Center.https://openriver.winona.edu/annualreportssld/1003/thumbnail.jp

Discovery of Cercosporamide, a Known Antifungal Natural Product, as a Selective Pkc1 Kinase Inhibitor through High-Throughput Screening

The Pkc1-mediated cell wall integrity-signaling pathway is highly conserved in fungi and is essential for fungal growth. We thus explored the potential of targeting the Pkc1 protein kinase for developing broad-spectrum fungicidal antifungal drugs through a Candida albicans Pkc1-based high-throughput screening. We discovered that cercosporamide, a broad-spectrum natural antifungal compound, but previously with an unknown mode of action, is actually a selective and highly potent fungal Pkc1 kinase inhibitor. This finding provides a molecular explanation for previous observations in which Saccharomyces cerevisiae cell wall mutants were found to be highly sensitive to cercosporamide. Indeed, S. cerevisiae mutant cells with reduced Pkc1 kinase activity become hypersensitive to cercosporamide, and this sensitivity can be suppressed under high-osmotic growth conditions. Together, the results demonstrate that cercosporamide acts selectively on Pkc1 kinase and, thus, they provide a molecular mechanism for its antifungal activity. Furthermore, cercosporamide and a β-1,3-glucan synthase inhibitor echinocandin analog, by targeting two different key components of the cell wall biosynthesis pathway, are highly synergistic in their antifungal activities. The synergistic antifungal activity between Pkc1 kinase and β-1,3-glucan synthase inhibitors points to a potential highly effective combination therapy to treat fungal infections