Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.
Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.
复制标题
受激相移声纳米滴增强万古霉素对耐甲氧西林金黄色葡萄球菌生物膜的功效
DOI：
10.2147/ijn.s134525
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发表时间：
2017
影响因子：
8
通讯作者：
Wang A
中科院分区：
文献类型：
--
作者：
Guo H;Wang Z;Du Q;Li P;Wang Z;Wang A
假体表面的细菌生物膜正在成为管理假体关节感染的一个日益关注的问题。生物膜固有的耐药性特征使得传统的抗菌治疗无效，翻修手术结局不确定。这种情况促使人们探索新的抗菌策略。超声微泡和万古霉素的协同作用已被提出作为生物膜根除的有效替代方案。本研究的目的是评估受激相移声纳米滴（ND）联合万古霉素的抗生物膜效果。我们制作了具有液体全氟戊烷核心的脂质相移ND。开发了一种新的ND相变模式，该模式将初始未聚焦的低强度脉冲超声持续5分钟，随后在37°C下孵育24小时。将耐甲氧西林金黄色葡萄球菌（MRSA）生物膜与万古霉素和NDs在杂交刺激下孵育。使用共聚焦激光扫描显微镜和扫描电子显微镜测定处理后的生物膜形态。刃天青测定用于量化针对MRSA生物膜细菌的杀菌功效。用超声和在37°C下加热顺序处理的ND在连续过程中实现了逐渐和实质性的ND蒸发和空化。刺激后的NDs能够对生物膜结构产生更强的破坏，其最佳特征是残留的圆弧边缘和更多的死菌。NDs与万古霉素联合应用可显著降低MRSA生物膜中细菌的代谢活性（P<0.05）。相移声微扰能通过一种新的刺激方式对MRSA生物膜产生显著的杀菌作用。声学ND在生物膜损伤方面优于微泡。这种抗生物膜策略可以单独使用，也可以作为传统抗生素的增强剂用于控制人工关节感染。
Bacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs) combined with vancomycin. We fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA) biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria. NDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs combined with vancomycin contributed to significantly decreasing the metabolic activity of bacteria in MRSA biofilms (P<0.05). Phase-shift acoustic NDs could exert a significant bactericidal effect against MRSA biofilms through a new stimulation mode. Acoustic NDs present advantages over microbubbles for biofilm damage. This anti-biofilm strategy could be used either alone or as an enhancer of traditional antibiotics in the control of prosthetic joint infections.