Dr. Douglas I. Johnson
Yeast Biofilm Formation and Virulence
Our lab studies the mechanisms by which environmental and cellular signals regulate biofilm formation in the pathogenic yeast Candida albicans. The ability of C. albicans to form biofilms on indwelling medical devices such as catheters is a major virulence factor for this organism. Experimentally, we utilize microplate-based morphology assays to screen small molecule libraries for inhibitors of biofilm formation. We have identified 21 molecules that can inhibit the ability of C. albicans to form biofilms and growth in a hyphal state. We also use classical and molecular genetics to identify the signaling pathways that are affected by these small molecule inhibitors. These molecules can inhibit multiple signaling pathways, including MAPK pathways and small GTPase pathways. The types of questions we will be addressing over the next five years include: (1) What are the molecular targets of these small molecule inhibitors in C. albicans?; (2) Can these molecules affect the ability of clinical isolates of C. albicans to form biofilms on indwelling medical devices?; and (3) Do these molecules inhibit C. albicans biofilm formation and virulence in mouse and rat models of candidiasis?.
Toenjes, K.A., B.C. Stark, K.M. Brooks, D.K. Butler, and D.I. Johnson. Inhibitors of cellular signaling are cytotoxic or block the budded-to-hyphal transition in the pathogenic yeast Candida albicans. J Med Microbiol. 2009 Jun;58(Pt 6):779-90.
Midkiff, J., N. Borochoff-Porte, D. White, and D.I. Johnson. Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways. PLoS ONE 2011 6:e25395.
Grald, A., P. Yargosz, S. Case, K. Shea, and D.I. Johnson. Small molecule inhibitors of biofilm formation in laboratory and clinical isolates of Candida albicans. J. Med. Microbiol. 2012. 69:109-114