Gram-Negative Bacteria Targeting AIE Photosensitizer for Selective Photodynamic Killing of Vibrio vulnificus

Abstract

Vibrio vulnificus is a highly virulent Gram-negative bacterium exhibiting extensive resistance to various antibiotics, presenting significant challenges for efficient and selective eradication. Recently, photosensitizer (PS)-based photodynamic therapy has emerged as an effective strategy against bacteria and biofilms. However, traditional PS struggles to penetrate the unique membrane structure of Gram-negative bacteria such as V. vulnificus, while avoiding traversal of the membrane barrier of eukaryotic cells. To address this issue, herein, a PS named BDTP with aggregation-induced emission properties was developed. BDTP can specifically target the DNA of V. vulnificus, but integrate into the cell membrane, preventing damage to the contents in eukaryotic cells due to its hydrophilic/lipophilic “Y-shaped” structural characteristics. In dark conditions, BDTP functions as an antibiotic, inhibiting bacterial proliferation. Upon white light stimulation, BDTP can induce phototoxic damage to the DNA of V. vulnificus and effectively inhibit/clear V. vulnificus biofilms. Additionally, the eukaryotic cell membrane barrier significantly reduces PS-induced damage to its nucleic acids. This strategy significantly promotes the healing of infected wounds in V. vulnificus-infected mice. Our work introduces the first PS targeting V. vulnificus-associated infections, demonstrating efficacy both in vitro and in vivo.