Abstract
The rapid proliferation of multidrug-resistant (MDR) bacterial infections has posed the serious health threats. Photodynamic therapy is considered one of the most promising therapeutic strategies for combating bacterial resistance. In the present study, we synthesized an unsymmetrical oligo-p-phenylene ethynylene (OPE), namely OPE3, and investigated its antimicrobial activity against gram-negative and gram-positive MDR bacteria in vitro and in vivo. The results showed that OPE3 had marked antibacterial activity against MDR bacteria under light irradiation conditions. OPE3 exerted a slightly greater effect on gram-positive bacteria than gram-negative bacteria. Biofilm assay results showed that OPE3 could not inhibit biofilm formation at sub-minimum inhibitory concentrations (MICs), whereas a significant decrease in preformed biofilms was observed when they were treated with OPE3 at concentrations ≥2 × MIC. OPE3 had no hemolytic activity or cytotoxicity in mammalian cells at low concentrations. In the mouse model of burn infection caused by Pseudomonas aeruginosa and Staphylococcus aureus, the treatment of infected wounds with OPE3 resulted in a significant dose-dependent reduction in the bacterial load and caused smaller skin lesions. In addition, the levels of the inflammatory cytokines TNF-α and IL-6 in the serum were also significantly reduced. The present study results indicate that OPE3 may serve as a potent antimicrobial molecule for the treatment of MDR bacterial infections.
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