Data_Sheet_1_Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo.docx

For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.

针对细菌感染的治疗，光动力抗菌化疗（PACT）具备绕过多重耐药性的优势。本研究中，通过将氨基苯基卟啉与碱性氨基酸L-鸟氨酸进行偶联，设计并合成了针对多重耐药性变形菌（MRPM）的新型阳离子光敏剂。报告了其在体外对MRPM的光失活效率，包括激光能量、摄取、最小抑菌浓度（MIC）和最小杀菌浓度（MBC）、剂量依赖性光失活效果、细胞膜完整性以及荧光成像的影响。采用感染MRPM的伤口小鼠模型对PACT进行了体内评估。光敏剂4d在7.81μM的浓度下，在光照条件下对MRPM表现出高光失活效率，并能通过杀菌作用加速伤口愈合。这些鸟氨酸-卟啉偶联物是治疗MRPM感染中PACT的潜在光敏剂。