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Study of the effect of antimicrobial peptide mimic, CSA‐13, on an established biofilm formed by Pseudomonas aeruginosa

机译:研究抗菌肽模拟物CSA-13对由铜绿假单胞菌形成的已建立生物膜的影响

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AbstractThe formation of a Pseudomonas aeruginosa biofilm, a complex structure enclosing bacterial cells in an extracellular polymeric matrix, is responsible for persistent infections in cystic fibrosis patients leading to a high rate of morbidity and mortality. The protective environment created by the tridimensional structure reduces the susceptibility of the bacteria to conventional antibiotherapy. Cationic steroid antibiotics (CSA)-13, a nonpeptide mimic of antimicrobial peptides with antibacterial activity on planktonic cultures, was evaluated for its ability to interact with sessile cells. Using confocal laser scanning microscopy, we demonstrated that the drug damaged bacteria within an established biofilm showing that penetration did not limit the activity of this antimicrobial agent against a biofilm. When biofilms were grown during exposure to shear forces and to a continuous medium flow allowing the development of robust structures with a complex architecture, CSA-13 reached the bacteria entrapped in the biofilm within 30 min. The permeabilizing effect of CSA-13 could be associated with the death of the bacteria. In static conditions, the compound did not perturb the architecture of the biofilm. This study confirms the potential of CSA-13 as a new strategy to combat persistent infections involving biofilms formed by P. aeruginosa.
机译:摘要铜绿假单胞菌生物膜的形成是一种复杂的结构,将细菌细胞包裹在细胞外聚合物基质中,是造成囊性纤维化患者持续感染的原因,导致高发病率和死亡率。由三维结构产生的保护性环境降低了细菌对常规抗生物疗法的敏感性。评估了阳离子类固醇抗生素(CSA)-13,它是一种对浮游生物具有抗菌活性的抗菌肽的非肽模拟物,其与无柄细胞相互作用的能力得到了评估。使用共聚焦激光扫描显微镜,我们证明了药物破坏了已建立的生物膜内的细菌,表明渗透并没有限制这种抗微生物剂对生物膜的活性。当生物膜在受到剪切力作用和连续的介质流动过程中生长时,可以形成具有复杂结构的坚固结构,CSA-13在30分钟内到达了被生物膜截留的细菌。 CSA-13的透化作用可能与细菌的死亡有关。在静态条件下,该化合物不会干扰生物膜的结构。这项研究证实了CSA-13作为对抗由绿脓杆菌形成的生物膜引起的持续感染的新策略的潜力。

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