Peng Xingrao, Luo Yong, Xu Tianzhi, Chen Zihan, Chen Peiyao, Hu Cong, Liu Shuang
School of Materials Science and Engineering, Wuhan University of Technology 122 Luoshi Road Wuhan Hubei 430070 China
State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University Changsha 410082 China.
RSC Adv. 2025 Jun 11;15(25):19751-19761. doi: 10.1039/d5ra02932e. eCollection 2025 Jun 10.
Herein, we report a pair of paenipeptin C'-based antimicrobial linear lipopeptides that significantly enhance bacterial inhibition through conjugation to antibiotics. When co-incubated with or , these peptides induce bacterial death. The antimicrobial peptides target negatively charged bacterial membranes electrostatic interactions, subsequently disrupting membrane integrity through aggregation and insertion, leading to membrane rupture and cytoplasmic leakage, as evidenced by bacterial morphology studies. Lipopeptides with longer alkyl chains penetrate deeper into the membrane structure, demonstrating stronger antibacterial effects. Additionally, the conjugated antibiotics may enhance bactericidal activity by inhibiting intracellular DNA gyrase. Therapeutic efficacy was further validated in a murine infected wound model. This work not only develops a class of broad-spectrum antimicrobial lipopeptides but also provides a novel strategy for developing antibiotic-conjugated antimicrobial peptides to enhance multiple antibacterial inhibition with minimal side effects.
在此，我们报道了一对基于派尼肽C'的抗菌线性脂肽，它们通过与抗生素结合显著增强了细菌抑制作用。当与或共同孵育时，这些肽会诱导细菌死亡。抗菌肽通过静电相互作用靶向带负电荷的细菌膜，随后通过聚集和插入破坏膜的完整性，导致膜破裂和细胞质泄漏，细菌形态学研究证明了这一点。具有较长烷基链的脂肽能更深入地穿透膜结构，显示出更强的抗菌效果。此外，结合的抗生素可能通过抑制细胞内DNA促旋酶来增强杀菌活性。在小鼠感染伤口模型中进一步验证了治疗效果。这项工作不仅开发了一类广谱抗菌脂肽，还为开发抗生素结合抗菌肽以增强多重抗菌抑制且副作用最小提供了一种新策略。
