Antimicrobial Efficacy of Photocaged β‐lapachone in Bacillus subtilis Biofilms

With the rise of antibiotic resistance within clinical settings, combating the growth of microbial biofilms presents a unique challenge. Biofilm‐inhabiting bacteria are embedded within a self‐produced, protective matrix, which can reduce the efficacy of treatment. The naturally derived product β‐lapachone is an appealing therapeutic agent that has been reported to inhibit biofilm growth. However, its off‐target toxicity and poor metabolic stability pose a significant hurdle for its application in vivo. Using a photo‐pharmacological approach via a coumarin‐based photocage, the reactivity of β‐lapachone can be tuned so it only becomes active once the photocage is removed. Here we report both the photo‐uncaging efficiency and the effective inhibition concentration of photocaged β‐lapachone within model Bacillus subtilis biofilms. Additionally, the mechanism of action is analyzed with results supporting catalase inhibition. This novel light‐activatable anti‐microbial has potential applications in medical settings to inhibit biofilm growth and provide synergistic treatment with traditional antibiotics.