A Water-Soluble Aggregation-Induced Emission Photosensitizer with Intrinsic Antibacterial Activity as an Antiplanktonic and Antibiofilm Therapeutic Agent

Photosensitizers (PS)s with aggregation-induced emission (AIE) properties have gained popularity in treating bacterial infections. However, most AIE PSs have poor water solubility and low selectivity, which greatly limit their applications in biological systems. Herein, we report a water-soluble and bacteria-targeting AIE PS, TPA-1, which showed minimum cytotoxicity towards human cells with and without light irradiation. Without light irradiation, TPA-1 acts as a narrow-spectrum antibacterial agent, eradicating planktonic S. aureus and inhibiting their biofilm formation. The mechanism study showed that TPA-1 targets S. aureus membrane, inhibits the supercoiling activity of S. aureus DNA gyrase, and causes downregulation of mulitple essential proteins. With light irradiation, TPA-1 showed excellent antiplanktonic and antibiofilm activities against S. aureus and P. aeruginosa by generating reactive oxygen species that cause membrane damage. Furthermore, TPA-1 under light irradiation can significantly reduce the number of viable bacteria in biofilms and promote wound healing in methicillin-resistant S. aureus (MRSA) and P. aeruginosa-infected mice models