Cec4-Derived Peptide Inhibits Planktonic and Biofilm-Associated Methicillin Resistant Staphylococcus epidermidis.
Cec4-Derived Peptide Inhibits Planktonic and Biofilm-Associated Methicillin Resistant Staphylococcus epidermidis.
复制标题
DOI：
10.1128/spectrum.02409-22
复制
发表时间：
2022-12-21
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
表皮葡萄球菌是定植于人类皮肤和粘膜表面的正常微生物群的一部分。以往的研究表明，S.表皮葡萄球菌的毒力较低，但近年来的研究证实其可从金黄色葡萄球菌获得高毒力，随着耐甲氧西林葡萄球菌的检出率的增加，表皮葡萄球菌的耐甲氧西林能力逐渐增强。表皮。它已成为移植物相关感染和医院获得性感染的主要病原体。在前期的研究中，我们对抗菌肽Cec 4（41个氨基酸）进行了修饰，得到了具有较好抗菌活性的Cec 4衍生肽C9（16个氨基酸）。对表皮的MIC值为8 μg/mL。该肽具有快速杀菌活性，且未检测到高水平的耐药性，对沙门氏菌表现出一定的抑制和根除能力。表皮生物膜用扫描电镜（SEM）和透射电镜（TEM）观察C9对细胞膜结构的损伤。此外，C9改变了S.表皮细胞膜的通透性、去极化水平、流动性和活性氧（ROS）的积累，并具有结合基因组DNA的能力。C9处理的细胞的转录谱的分析揭示了参与细胞壁和核糖体生物合成，膜蛋白转运，氧化应激和DNA转录调控的基因的变化。同时，C9对小鼠的半数致死量超过128 mg/kg，腹腔给药64 mg/kg对小鼠肝脏和肾脏的毒性较小。C9对小鼠菌血症模型也有一定的治疗作用。因此，C9有可能成为抗沙门氏菌的候选药物。epidermidis，其具有进一步开发为抗菌治疗剂的潜力。重要性S.表皮葡萄球菌是移植物相关性感染和医院获得性感染的重要病原体之一。日益严重的抗生素耐药性问题以及细菌致病性的出现，突出了对具有新作用模式的抗菌剂的需求。在过去的30年中，抗菌肽作为抗生素的理想替代品已被广泛研究，我们在这里报告衍生肽C9的特征在于快速杀菌和抗菌膜活性，通过作用于细胞膜或细胞组分的多个非特异性靶点来避免耐药性的发展。此外，它对S.体内表皮感染。该研究为C9作为一种有效的候选抗生素的进一步开发和应用提供了理论基础。
Staphylococcus epidermidis is part of the normal microbiota that colonizes the skin and mucosal surfaces of human beings. Previous studies suggested that S. epidermidis possessed low virulence, but recent studies confirmed that it can acquire high virulence from Staphylococcus aureus and with the increasing detection of methicillin-resistant S. epidermidis. It has become a major pathogen of graft-associated and hospital-acquired infections. In previous studies, we modified the antimicrobial peptide Cec4 (41 amino acids) and obtained the derived peptide C9 (16 amino acids) showing better antimicrobial activity against S. epidermidis with an MIC value of 8 μg/mL. The peptide has rapid bactericidal activity without detectable high-level resistance, showing certain inhibition and eradication ability on S. epidermidis biofilms. The damage of cell membrane structures by C9 was observed by scanning emission microscopy (SEM) and transmission electron microscopy (TEM). In addition, C9 altered the S. epidermidis cell membrane permeability, depolarization levels, fluidity, and reactive oxygen species (ROS) accumulation and possessed the ability to bind genomic DNA. Analysis of the transcriptional profiles of C9-treated cells revealed changes in genes involved in cell wall and ribosome biosynthesis, membrane protein transport, oxidative stress, and DNA transcription regulation. At the same time, the median lethal dose of C9 in mice was more than 128 mg/kg, and the intraperitoneal administration of 64 mg/kg was less toxic to the liver and kidneys of mice. Furthermore, C9 also showed a certain therapeutic effect on the mouse bacteremia model. In conclusion, C9 may be a candidate drug against S. epidermidis, which has the potential to be further developed as an antibacterial therapeutic agent. IMPORTANCE S. epidermidis is one of the most important pathogens of graft-related infection and hospital-acquired infection. The growing problem of antibiotic resistance, as well as the emergence of bacterial pathogenicity, highlights the need for antimicrobials with new modes of action. Antimicrobial peptides have been extensively studied over the past 30 years as ideal alternatives to antibiotics, and we report here that the derived peptide C9 is characterized by rapid bactericidal and antibiofilm activity, avoiding the development of resistance by acting on multiple nonspecific targets of the cell membrane or cell components. In addition, it has therapeutic potential against S. epidermidis infection in vivo. This study provides a rationale for the further development and application of C9 as an effective candidate antibiotic.
登录
查看更多内容
影响因子：
--
作者：
Overton IM;Graham S;Gould KA;Hinds J;Botting CH;Shirran S;Barton GJ;Coote PJ
通讯作者：
Coote PJ
影响因子：
3.5
作者：
Guo, Jinfeng;Li, Xu;Li, Kaixiong
通讯作者：
Li, Kaixiong
DOI：
10.1016/s0304-4165(00)00133-1
发表时间：
2000-10-18
影响因子：
3
作者：
Brandenberger, M;Tschierske, M;Berger-Bächi, B
通讯作者：
Berger-Bächi, B
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
3.8
作者：
Albano, Mariana;Crulhas, Bruno Pereira;Fernandes Junior, Ary
通讯作者：
Fernandes Junior, Ary