PROJECT SUMMARY Acne vulgaris is a skin inflammatory condition affecting 80% of young adults and can frequently induce permanent disfigurement even with appropriate treatment. Acne is caused by C. acnes in the setting of hormonal changes and sebum induction that accompany adolescence. The mainstay of therapeutics consist of eradicating C. acnes and reducing inflammation. However, treatment is prolonged (usually 4-8 weeks in duration) and has been associated in recent years with the emergence of antibiotic resistance. Resistance to two first line antibiotics clindamycin and erythromycin currently stands at 30-50%. This severe situation highlights an unmet need for novel and more effective treatment options. This phase I STTR proposal, through a partnership between the George Liu lab and Pulsethera Inc, aims to amplify these initial findings and to design a prototype for treatment of multi-drug resistant acne infections. The PI Ji-Xin Cheng (PhD) is an expert of Biophotonics. The co-PI George Liu (MD PhD) is a pioneer in the study of chromophores including catalase in bacteria and was the first to uncover staphyloxanthin’s anti-oxidant property in S. aureus. Liu and Cheng have an ongoing collaboration in developing novel antimicrobial phototherapies (Science Advances, 2020, 7:1903117). A recent collaboration between George Liu lab at UCSD and Ji-Xin Cheng lab at Boston University found that catalase, naturally expressed in a broad spectrum of bacterial (both gram-negative and gram-positive) and fungal species, can be inactivated by a blue light LED and more effectively by pulsed blue light (manuscript in prep). Consequently, we have observed that photo-inactivation of catalase effectively sensitizes pathogens including C. acne to very low concentration of hydrogen peroxide. The team’s central hypothesis is that photo-inactivation of catalase is able to sensitize C. acne pathogens to ROS-producing immune cells and antimicrobial agents. To test this hypothesis, we will first develop a catalase photo-inactivation prototype and validate its efficiency in killing C. acne in synergy with hydrogen peroxide (aim 1). We will then determine the efficacy of catalase photo-inactivation coupled with peroxide in the treatment of acne in vivo in an animal model (aim 2). By accomplishing the proposed studies, it is our expectation that accelerated elimination of the pro-inflammatory C. acnes will lead to improved outcome and obviate the need for long courses of antibiotics that are the cause of antibiotic resistance.