Dong Ying, Xu Yaling, Li Pan, Wang Chuanqing, Cao Yun, Yu Jialin
Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China.
Department of Pediatrics, Children's Hospital of Fudan University, Shanghai, 201102, China.
Int J Med Microbiol. 2017 Sep;307(6):321-328. doi: 10.1016/j.ijmm.2017.06.001. Epub 2017 Jun 11.
Biofilms are difficult to eradicate due to their resistance to antibiotics and host immune cells. Ultrasound microbubbles have emerged as a new treatment modality with the underlying mechanisms largely unknown. In this study, we exposed 24-h-old Staphylococcus epidermidis biofilms established in OptiCell™ chambers to ultrasound in combination with microbubbles, and investigated the activities of vancomycin and neutrophils against S. epidermidis biofilms after treatment. The antibiofilm mechanims of ultrasound microbubbles were explored in terms of bacterial permeability and biofilm-associated gene expression. After treatment of ultrasound (1MHz, 0.5W/cm, 50% duty cycle) combined with microbubbles in the concentration of 1% and 4% (v/v) for 5min, bacterial permeability to extracellular fluorescent dyes was enhanced and the expression of icaA was down-regulated while that of agrB and RNAIII up-regulated. Post-treatment biofilms were more sensitive to vancomycin by demonstrating reduced biomass than those exposed to vancomycin alone (P<0.05). The phagocytosis, oxidative burst activity as well as chemotaxis of neutrophils in response to biofilms were also significantly increased. The bioeffect of ultrasound combined with microbubbles was generally more significant than that of ultrasound alone, and dependent on microbubble concentration. This study demonstrated that ultrasound combined with microbubbles could enhance the activities of antibiotics and neutrophils against biofilms possibly via mechanical and biochemical mechanisms, and may provide an efficient and non-invasive antibiofilm alternative apart from chemical and biological approaches.
生物膜因其对抗生素和宿主免疫细胞具有抗性而难以根除。超声微泡已成为一种新的治疗方式，但其潜在机制大多未知。在本研究中，我们将在OptiCell™培养室中形成的24小时龄表皮葡萄球菌生物膜暴露于超声联合微泡环境下，并研究了万古霉素和中性粒细胞在处理后对表皮葡萄球菌生物膜的活性。从细菌通透性和生物膜相关基因表达方面探究了超声微泡的抗生物膜机制。在以1%和4%（v/v）的浓度将超声（1MHz，0.5W/cm，50%占空比）与微泡联合处理5分钟后，细菌对细胞外荧光染料的通透性增强，icaA的表达下调，而agrB和RNAIII的表达上调。处理后的生物膜对万古霉素更敏感，与单独暴露于万古霉素的生物膜相比，其生物量减少（P<0.05）。中性粒细胞对生物膜的吞噬作用、氧化爆发活性以及趋化性也显著增加。超声联合微泡的生物效应总体上比单独超声更显著，且依赖于微泡浓度。本研究表明，超声联合微泡可能通过机械和生化机制增强抗生素和中性粒细胞对生物膜的活性，并且除了化学和生物学方法外，可能提供一种高效且无创的抗生物膜替代方法。
