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Title: “Antimicrobial Phototherapy: Mechanisms and Translation”

Advisory Committee: Mo Khalil, PhD – BU BME (Chair) Ji-Xin Cheng, PhD – BU BME, ECE, MSE (Advisor) Jerome Mertz, PhD – BU BME, ECE, Physics Shyam Erramilli, PhD – BU Physics, BME, MSE George Liu, MD/PhD – UCSD School of Medicine

Abstract: Over the past few decades, the global healthcare community has witnessed the rise and spread of drug resistance across a broad spectrum of both bacterial and fungal pathogens, due to a combination of medical overuse and slowing pharmaceutical drug development. As a result, technology like blue light phototherapy has emerged as novel non-drug reliant alternatives based on their broad-spectrum antimicrobial capabilities. However, despite this known antimicrobial activity, questions remain regarding the overall mechanisms and downstream effects of antimicrobial blue light, as well as its potential translatability to clinical settings.

In this thesis, we have extensively investigated the role of antioxidant catalase within antimicrobial blue light, observing the impact of antioxidant presence on blue light’s antimicrobial activity and demonstrating the significant role that catalase photodeactivation plays in inducing broad spectrum ROS sensitization across bacteria. Based on these results, we reveal the translatability of this blue light phototherapy to fight against bacterial infections by utilizing blue light to potentiate bacterial pathogens against conventional antibiotics, the host immune system, and within an in vivo murine model. Next, we extend our observations on the effects of antimicrobial blue light to more complex eukaryotic fungal pathogens, discovering that the catalase deactivating effects of blue light can suppress the hyphae forming capabilities of pathogenic Candida fungi through lipogenesis inhibition and demonstrating the translatability of this technology to target Candida skin infections within an in vivo murine model and an ex vivo human skin model. Finally, we further explore the translatability of this technology by synergizing the effects of catalase deactivating blue light with the clinically relevant topical antibiotic silver sulfadiazine within both in vitro and in vivo environments, establishing a commonly used topical clinical agent that can be used to synergize with the technology.