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首页> 外文期刊>Antibiotics >Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients
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Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients

机译：抑制囊性纤维化患者病原体形成的生物膜形成的肽的抗生物膜和免疫调节活性

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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.
机译：囊性纤维化（CF）患者通常由于铜绿假单胞菌和洋葱伯克霍尔德菌（Bccholderia cepacia complex）种类而获得慢性呼吸道感染。这些细菌在CF肺中以称为生物膜的多细胞聚集体生长。生物膜表现出对常规抗生素的增强（适应性）抗性，目前尚无可用的生物膜特异性疗法。使用塑料粘附，羟基磷灰石和流通池生物膜模型，以及共焦和扫描电子显微镜，证明了抗生物膜肽1018可以防止生物膜形成，消除成熟的生物膜并杀死由广泛的铜绿假单胞菌和铜绿假单胞菌形成的生物膜。临床分离菌。设计了新的肽衍生物，与其亲本肽1018相比，它们对铜绿假单胞菌生物膜显示相似或降低的抗生物膜活性，但对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活性增强。此外，这些新的肽衍生物中的一些保留了1018的免疫调节活性，因为它们诱导了趋化因子单核细胞趋化蛋白1（MCP-1）的产生并抑制了脂多糖介导的肿瘤坏死因子-α（TNF-α）的产生。人外周血单个核细胞（PBMC），并且对这些细胞无毒。肽1018及其衍生物为CF患者的慢性生物膜感染和肺炎性肺疾病的治疗提供了有前途的线索。

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