Author(s)

Amanda J. Searle, Vern Winston, Gene M. Scalarone

Department of Biological Science, Idaho State University, Idaho, USA.

Blastomyces dermatitidis is a thermally dimorphic fungus that causes the disease blastomycosis. Currently there are a limited number of effective treatments, many of which have harsh side effects. Chitin, a component of the fungal cell wall is often broken down and recycled for cell wall remodeling and growth. Chitinase is the digestive enzyme capable of chitin hydrolysis. By inhibiting the chitinase we predicted that cells wouldn’t be able to divide and multiply normally, thereby leading to possible anti-fungal treatments. For this study we modeled the structure of B. dermatitidis chitinase, using homology modeling. By predicting a three-dimensional structure we were able to do additional analyses of the active site of the chitinase and predict the binding of a possible small molecule, acetazolamide, in silico. This binding allowed us to predict that this molecule might be capable of inhibiting the chitinase of B. dermatitidis. This inhibition was tested in vivo. No difference in the growth curves of the test and control organisms was observed, however there was a difference within the cell walls of the yeast cells. The cell walls appeared thicker with additional differences in cell wall orderly growth. These changes are consistent with changes that may occur as B. dermatitidis chitinases are inhibited.

Blastomyces dermatitidis; Chitinase; Homology Modeling; Acetazolamide; Inhibition

Searle, A. , Winston, V. and Scalarone, G. (2012) Blastomyces dermatitidis: Chitinase Homology Model, in Silico Docking, and Inhibition Assay. Open Journal of Medical Microbiology, 2, 1-7. doi: 10.4236/ojmm.2012.21001.