A Conjugated Oligomer with Drug Efflux Pump Inhibition and Photodynamic Therapy for Synergistically Combating Resistant Bacteria

Abstract

High expression of drug efflux pump makes antibiotics ineffective against bacteria, leading to drug-resistant strains and even the emergence of "superbugs". Herein, we design and synthesize a dual functional o-nitrobenzene (NB)-modified conjugated oligo-polyfluorene vinylene (OPFV) photosensitizer, OPFV-NB, which can depress efflux pump activity and also possesses photodynamic therapy (PDT) for synergistically overcoming drug-resistant bacteria. Upon light irradiation, the OPFV-NB can produce aldehyde active groups to covalently bind outer membrane proteins, such as tolerant colicin (TolC), blocking drug efflux of bacteria. The minimum inhibitory concentration of antibiotic model chloramphenicol (CHL) is reduced about 64 times, significantly resensitizing drug-resistant bacteria to antibiotics. Also, the probe can produce highly efficient reactive oxygen species (ROS) under light irradiation. Consequently, the unimolecular OPFV-NB-based system demonstrates insusceptibility to antibiotic resistance while maintaining significant antimicrobial effects (100%) against drug-resistant bacteria. More importantly, in vivo assays corroborate that the combined system greatly accelerates wound healing by eradicating the bacterial population, dampening inflammation, and promoting angiogenesis. Overall, the OPFV-NB not only counteracts antibiotic resistance but also holds tremendous PDT efficiency, which provides a promising therapeutic strategy for combating drug-resistant bacteria and treating bacteria-infected wounds.

Keywords: antibiotic resistance; conjugated oligomer; efflux pump; photodynamic antibacterial; synergistic treatment; wound healing.