Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients.
Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients.
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DOI：
10.3390/antibiotics3040509
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Hancock RE
中科院分区：
文献类型：
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作者：
de la Fuente-Núñez C;Mansour SC;Wang Z;Jiang L;Breidenstein EB;Elliott M;Reffuveille F;Speert DP;Reckseidler-Zenteno SL;Shen Y;Haapasalo M;Hancock RE
囊性纤维化（CF）患者经常由于铜绿假单胞菌和洋葱伯克霍尔德氏菌复合体（Bcc）物种而获得慢性呼吸道感染。在CF肺中，这些细菌生长为称为生物膜的多细胞聚集体。生物膜表现出对常规抗生素的增加的（适应性）抗性，并且目前没有可用的生物膜特异性疗法。使用塑料粘附、羟基磷灰石和流动池生物膜模型，结合共聚焦和扫描电子显微镜，证明抗生物膜肽1018防止生物膜形成，根除成熟生物膜并杀死由广泛的铜绿假单胞菌和B形成的生物膜。新洋葱属临床分离株。设计了新的肽衍生物，与其亲本肽1018相比，其显示出针对铜绿假单胞菌生物膜的相似或降低的抗生物膜活性，但针对由革兰氏阳性细菌耐甲氧西林金黄色葡萄球菌形成的生物膜的活性增加。此外，这些新肽衍生物中的一些保留了1018的免疫调节活性，因为它们诱导人外周血单核细胞（PBMC）产生趋化因子单核细胞趋化蛋白-1（MCP-1）并抑制脂多糖介导的肿瘤坏死因子-α（TNF-α）产生，并且对这些细胞无毒。肽1018及其衍生物为治疗CF患者的慢性生物膜感染和炎症性肺病提供了有希望的线索。
Cystic fibrosis (CF) patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive) resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1) and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α) production by human peripheral blood mononuclear cells (PBMC) and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients.