Antimicrobial Efficacy of Photocaged β-Lapachone in Bacillus subtilis Biofilms

Abstract

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.