Stereoisomeric AIE Photosensitizers for Biofilm Inhibition and Host-Directed Elimination of Intracellular Multidrug-Resistant Bacteria

Bacteria can form biofilms on their surfaces or escape from the phagosomes and multiply in the cytoplasm to become intracellular bacteria, presenting a challenge for antibiotics to reach the bacterial cells and consequently making treatment difficult. In light of this, we employed two cis-trans molecules with aggregation-induced emission (AIE) properties, (E)- and (Z)-TPE-EPy, which have the ability to hinder Gram-positive (G+) bacteria Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) biofilm formation by reactive oxygen species (ROS) and eradicate intracellular MRSA by host-directed therapy (HDT). These molecules can bind to the intracellular bacteria, target mitochondria, and generate ROS in situ, reduce mitochondrial membrane potential, subsequently induce autophagy to clear intracellular bacteria, and reduce inflammation. Also, these AIE luminogens (AIEgens) can promote the healing of wounds with MRSA infection by killing bacteria and regulating wound inflammation. Our findings shed a light on the potential application of AIEgens in antimicrobial therapy and developed an available strategy against intracellular bacteria.