College of Pharmacy, Hubei University of Medicine, Shiyan 442000, P. R. China.
J Mater Chem B. 2019 Feb 21;7(7):1087-1095. doi: 10.1039/c8tb03094d. Epub 2019 Jan 25.
Photodynamic therapy (PDT) has become an effective antibiosis method for overcoming antibiotic resistance. In this study, we developed a versatile bacterial membrane-binding chimeric peptide PpIX-[PEG-(KLAKLAK)] (denoted as PPK) by conjugating a photosensitizer protoporphyrin IX (PpIX) with an antimicrobial peptide (KLAKLAK) (KLA) for effective photodynamic inactivation of bacteria. The chimeric peptide PPK with positively charged properties and an α-helical conformation could rapidly bind to microbial cells through electrostatic interactions and membrane insertion. Moreover, PPK could disrupt the bacterial membrane and further elicit lipid bilayer leakage to kill bacteria by toxic reactive oxygen species (ROS) generated by PpIX under 660 nm light. In vitro experiments demonstrated that cationic PPK possessed excellent antimicrobial activity against both Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). Afterward, PPK also exhibited perfect therapeutic effects on S. aureus-infected mice without any systemic side effects. This chimeric peptide PPK will show great potential for photodynamic antibiosis.
光动力疗法（PDT）已成为克服抗生素耐药性的一种有效抗菌方法。在这项研究中，我们通过将光敏剂原卟啉 IX（PpIX）与抗菌肽（KLAKLAK）（KLA）缀合，开发了一种多功能细菌膜结合嵌合肽 PpIX-[PEG-（KLAKLAK）]（表示为 PPK），以有效光动力灭活细菌。带正电荷性质和α-螺旋构象的嵌合肽 PPK 可以通过静电相互作用和膜插入快速结合微生物细胞。此外，PPK 可以通过 PpIX 在 660nm 光下产生的毒性活性氧（ROS）破坏细菌膜并进一步引发脂质双层渗漏杀死细菌。体外实验表明，阳离子 PPK 对革兰氏阳性菌金黄色葡萄球菌（S. aureus）和革兰氏阴性菌大肠杆菌（E. coli）均具有优异的抗菌活性。之后，PPK 还在没有任何全身副作用的情况下对金黄色葡萄球菌感染的小鼠表现出完美的治疗效果。这种嵌合肽 PPK 将在光动力抗菌方面显示出巨大的潜力。
