Theses and Dissertations

Advisor

Gordon, Donna M.

Committee Member

Thornton, Justin A.

Committee Member

Lu, Shien

Date of Degree

5-10-2024

Original embargo terms

Visible MSU only 2 years

Document Type

Graduate Thesis - Campus Access Only

Major

Biological Sciences

Degree Name

Master of Science (M.S.)

College

College of Arts and Sciences

Department

Department of Biological Sciences

Abstract

Occidiofungin is an antifungal compound that targets the conserved cytoskeletal protein, actin. Despite >90% amino acid conservation between fungal actin proteins, sensitivity to occidiofungin has been shown to vary with C. albicans, F. oxysporum, and P. digitatum exhibiting a resistant profile relative to S. cerevisiae. To determine whether differences in the amino acid sequences of actin contribute to differences in occidiofungin susceptibility, we expressed the actin gene from these fungal organisms in the ACT1 S. cerevisiae shuffle strain. Functionality of actin gene products was determined by measuring growth kinetics, actin protein levels, nuclear position, and actin cable formation. Results demonstrated functional complementation for all actin orthologs. Analysis of occidiofungin susceptibility found that fungal actin ortholog expression resulted in a similar sensitivity profile as the wildtype S. cerevisiae. These findings suggest that amino acid differences in actin are not directly responsible for the resistance to occidiofungin identified for these fungal organisms.

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