Discipline of Infectious Diseases and Immunology, Sydney Medical School, Faculty of Medicine and Health , The University of Sydney , New South Wales 2006 , Australia.
Sydney School of Pharmacy, Faculty of Medicine and Health , The University of Sydney , New South Wales 2006 , Australia.
Mol Pharm. 2019 Apr 1;16(4):1723-1731. doi: 10.1021/acs.molpharmaceut.9b00080. Epub 2019 Feb 22.
Antibiotic resistance in pathogenic bacteria has emerged as a big challenge to human and animal health and significant economy loss worldwide. Development of novel strategies to tackle antibiotic resistance is of the utmost priority. In this study, we combined glutathione (GSH), a master antioxidant in all mammalian cells, and nitric oxide, a proven biofilm-dispersing agent, to produce GSNO. The resazurin biofilm viability assay, crystal violet biofilm assay, and confocal microscopy techniques showed that GSNO disrupted biofilms of both P. aeruginosa PAO1 and multidrug resistant A. baumaunii (MRAB 015069) more efficiently than GSH alone. In addition, GSNO showed a higher reduction in biofilm viability and biomass when combined with antibiotics. This combination treatment also inhibited A. baumaunii (MRAB 015069) growth and facilitated human foreskin fibroblast (HFF-1) confluence and growth simultaneously. A potentially inhalable GSNO powder with reasonable aerosol performance and antibiofilm activity was produced by spray drying. This combination shows promise as a novel formulation for treating pulmonary bacterial infections.
在全球范围内，病原菌的抗生素耐药性已经成为人类和动物健康以及重大经济损失的一大挑战。开发新的策略来应对抗生素耐药性是当务之急。在这项研究中，我们将谷胱甘肽（GSH）——所有哺乳动物细胞中的主要抗氧化剂，和一氧化氮——一种已被证实的生物膜分散剂，结合起来生成 GSNO。试卤灵生物膜活性测定、结晶紫生物膜测定和共聚焦显微镜技术表明，GSNO 比单独的 GSH 更有效地破坏铜绿假单胞菌 PAO1 和多药耐药鲍曼不动杆菌（MRAB 015069）的生物膜。此外，当与抗生素联合使用时，GSNO 显示出更高的生物膜存活率和生物量降低。这种联合治疗还抑制了鲍曼不动杆菌（MRAB 015069）的生长，并同时促进人包皮成纤维细胞（HFF-1）的融合和生长。通过喷雾干燥生产了一种具有合理气溶胶性能和抗生物膜活性的潜在可吸入 GSNO 粉末。这种联合治疗为治疗肺部细菌感染提供了一种新的制剂选择。
