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.

耐多药 (MDR) 细菌感染的迅速扩散已构成严重的健康威胁。光动力疗法被认为是对抗细菌耐药性的最有希望的治疗策略之一。在本研究中，我们合成了一种不对称的低聚对亚苯基乙炔（OPE），即 OPE3，并在体外和体内研究了其对革兰氏阴性和革兰氏阳性 MDR 细菌的抗菌活性. 结果表明，OPE3在光照条件下对MDR细菌具有显着的抗菌活性。OPE3 对革兰氏阳性菌的影响略大于革兰氏阴性菌。生物膜测定结果表明，OPE3 在亚最低抑菌浓度 (MIC) 下不能抑制生物膜形成，而当它们用浓度≥2 × MIC 的 OPE3 处理时，观察到预形成的生物膜显着减少。OPE3 在低浓度的哺乳动物细胞中没有溶血活性或细胞毒性。在铜绿假单胞菌和金黄色葡萄球菌引起的烧伤感染小鼠模型中，用 OPE3 治疗感染的伤口导致细菌负荷的显着剂量依赖性降低，并导致较小的皮肤损伤。此外，血清中炎性细胞因子TNF-α和IL-6的水平也显着降低。目前的研究结果表明，OPE3 可作为治疗 MDR 细菌感染的有效抗菌分子。