Dr. Douglas I. Johnson

Professor

Signaling Pathways Regulating Yeast Morphogenesis 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 other small molecules inhibit biofilm formation through the inhibition of the budded-to-hyphal transition in C. albicans?; (2) What are the molecular targets of these small molecule inhibitors?; (3) Do these molecules inhibit C. albicans biofilm formation and virulence in mouse and rat models of candidiasis?; and (4) Can these molecules affect the ability of clinical isolates of C. albicans to form biofilms on indwelling medical devices.

BACKGROUND

Dr. Johnson received his Ph.D. degree in 1983 from Purdue University under the direction of Dr. Ronald Somerville. After further postdoctoral research at Purdue University and with Dr. John Pringle at the University of Michigan, he joined the faculty in Microbiology and Molecular Genetics in 1988.

LAB MEMBERS

John Midkiff
        Graduate Student

SELECTED PUBLICATIONS

vandenBerg A.L., Ibrahim A.S., Edwards J.E. Jr, Toenjes K.A., Johnson D.I. Cdc42p GTPase regulates the budded-to-hyphal-form transition and expression of hypha-specific transcripts in Candida albicans. Eukaryotic Cell. 2004 Jun;3(3):724-734

Toenjes, K.A., S. Munsee, A. Ibrahim, R. Jeffrey, J.E. Edwards, Jr., D. I. Johnson. Small molecule inhibitors of the budded-to-hyphal-form transition in the pathogenic yeast Candida albicans. Antimicrob. Agents Chemother. 2005. 49:963-972.

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.