Masters Theses

Date of Award

12-2025

Degree Type

Thesis

Degree Name

Master of Science

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Gladys Alexandre

Committee Members

Heidi Goodrich-Blair, Brad Binder

Abstract

The demand for novel models and molecular techniques to better understand microbial pathogenesis has been motivated by the rising incidence of bacterial and fungal infections worldwide as well as the development of antibiotic and antifungal drug resistance. This study investigated the function of virulence-related genes and host-pathogen interactions using Candida glabrata, Candida albicans, and entomopathogenic Xenorhabdus species. The study sought to analyze the functions of STE11 and CHO1, examine virulence in Manduca sexta larvae, and evaluate MAPK signalling using molecular genetic approaches, functional complementation, western blotting, and non-mammalian infection models.

A truncation mutant of C. glabrata STE11 (STE11ΔN346) was successfully constructed and expressed via an episomal vector, pGRB2.1. Western blot analysis indicated that the truncation did not alter MAPK activation, suggesting a divergence from C. albicans regulatory pathways. Functional complementation in Saccharomyces cerevisiae cho1Δ mutants confirmed that CgCHO1 encodes a phosphatidylserine (PS) synthase, highlighting its conserved role in lipid biosynthesis and stress adaptation.

The M. sexta infection model successfully recapitulated virulence phenotypes observed in murine models, including the reduced virulence of C. albicans STE11ΔN467 mutants. The model was subsequently applied to assess the entomotoxic potential of Xenorhabdus species, revealing strain-specific differences in virulence and supporting the broader utility of this model in studying host-pathogen interactions across microbial kingdoms.

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