Project Summary The project will establish honeybee larvae as a model for microbial pathogenesis, identify antimicrobial proteins, and foster collaboration between the Rowley (INBRE) and Van Leuven (COBRE) laboratories. Vulvovaginal candidiasis (VVC) is a prevalent condition affecting 75% of women worldwide and is often caused by Candida species of yeast. Understanding the pathogenesis of VVC has been hampered by the lack of a model organism that mimics the acidic pH and predominance of Lactobacillus species in the human vaginal mucosa. The project innovation lies in the use of honeybee larvae as a novel insect model for VVC and integrates the complementary expertise of the Rowley and Van Leuven laboratories. INBRE investigator Rowley and COBRE investigator Van Leuven specialize in microbial pathogenesis and microbiomes. Both investigators use insect models and have realized the unique collaborative opportunities presented by their respective research programs to develop and test a novel insect model of the human vaginal tract. The research will leverage the unique characteristics of honeybee larvae, such as conserved innate immune mechanisms and midgut acidification by Lactobacillus species. The project studies the pathogenicity of Candida yeasts, the disease-protective role of Lactobacillus species, and investigates novel antimicrobial compounds. The project has three Specific Aims: 1- Develop the collaboration between INBRE investigator Rowley and COBRE investigator Van Leuven; 2 - COBRE investigator Van Leuven will develop honeybee larvae as a model system for Candida pathogenesis; and 3 - INBRE investigator Rowley will identify antimicrobial proteins produced by Lactobacillus that are active against pathogens. The project will make extensive use of PUI undergraduate student researchers in all stated research aims. Both laboratories are committed to providing technical training, mentorship, and supervision to all students involved in the project to ensure high standards of reproducibility, rigor, and safety. In summary, the research adopts an innovative and collaborative approach, utilizing the honeybee model to advance understanding and potentially unveil novel therapeutic approaches for VVC.