Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo

Area of Science:

• Biochemistry
• Microbiology
• Materials Science

Background:

• Intracellular bacteria, particularly multidrug-resistant (MDR) pathogens, pose significant challenges to conventional antibiotic therapies due to their protected location within host cells.
• Existing antibiotics often struggle to penetrate host cells and effectively eliminate internalized bacteria, leading to persistent infections and disease dissemination.

Purpose of the Study:

• To investigate the potential of novel aggregation-induced emission luminogens (AIEgens) as a new class of therapeutic agents against intracellular and extracellular bacteria.
• To evaluate the bactericidal efficacy, mechanism of action, and resistance potential of AIEgens against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA).

Main Methods:

• Synthesis and characterization of functionalized AIEgens (TBPs) with broad-spectrum bactericidal properties.
• Assessment of AIEgen activity against both extracellular and internalized Gram-positive bacteria.
• Investigation of the mechanism of bacterial killing, including reactive oxygen species (ROS) generation and autophagy induction.
• In vivo efficacy evaluation of AIEgens compared to vancomycin in a murine model of MRSA infection.

Main Results:

• AIEgens (TBPs) demonstrated potent bactericidal activity against extracellular and internalized Gram-positive pathogens, including MDR strains.
• TBPs induced bacterial death through ROS-mediated membrane damage, independent of light irradiation, and without apparent development of resistance.
• AIEgens effectively promoted the clearance of internalized bacteria via mitochondria-dependent autophagy.
• In vivo studies showed comparable efficacy of TBPs to vancomycin against MRSA infections.

Conclusions:

• AIEgens represent a promising new therapeutic avenue for combating challenging bacterial infections, including those caused by MDR pathogens.
• The dual action of AIEgens against extracellular and intracellular bacteria, coupled with their ability to evade resistance mechanisms, highlights their therapeutic potential.
• Further development of AIEgens could lead to novel treatments for persistent and difficult-to-treat bacterial infections.