Rational Design of β‑Carboline Photosensitizers for Combating Multidrug-Resistant Bacterial Infections

The misuse of antibiotics has accelerated the emergence of multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), creating an urgent need for novel antimicrobial strategies. Antimicrobial photodynamic therapy, which employs light-activated photosensitizers to generate reactive oxygen species (ROS), is promising since it kills both sensitive and resistant pathogens without inducing resistance. β-Carbolines, a class of natural alkaloids with notable antimicrobial potential, have mostly been studied for cancer therapy and rarely adapted as antibacterial photosensitizers. Here, we report a β-carboline-derived photosensitizer (<i><b>CabPT</b></i>) incorporating a quaternary ammonium group for bacterial targeting and a triphenylamine moiety to enhance ROS generation. <i><b>CabPT</b></i> produced strong ROS under white-light irradiation, exhibited excellent photostability, and showed low dark cytotoxicity. <i>In vivo</i>, <i><b>CabPT</b></i>-mediated phototherapy effectively treated MRSA-infected wounds, accelerating healing and promoting collagen deposition. This work demonstrates the rational design of β-carboline photosensitizers for targeting drug-resistant bacterial infections, offering a promising path for next-generation antimicrobial therapeutics.