Ulrey Robert K, Barksdale Stephanie M, Zhou Weidong, van Hoek Monique L
School of Systems Biology, George Mason University, Manassas, Virginia, USA.
BMC Complement Altern Med. 2014 Dec 16;14:499. doi: 10.1186/1472-6882-14-499.
Bacteria within a biofilm are phenotypically more resistant to antibiotics, desiccation, and the host immune system, making it an important virulence factor for many microbes. Cranberry juice has long been used to prevent infections of the urinary tract, which are often related to biofilm formation. Recent studies have found that the A-type proanthocyanidins from cranberries have anti-biofilm properties against Escherichia coli.
Using crystal violet biofilm staining, resazurin metabolism assays, and confocal imaging, we examined the ability of A-type proanthocyanidins (PACs) to disrupt the biofilm formation of Pseudomonas aeruginosa. We used mass spectrometry to analyze the proteomic effects of PAC treatment. We also performed synergy assays and in vitro and in vivo infections to determine whether PACs, alone and in combination with gentamicin, could contribute to the killing of P. aeruginosa and the survival of cell lines and G. mellonella.
Cranberry PACs reduced P. aeruginosa swarming motility. Cranberry PACs significantly disrupted the biofilm formation of P. aeruginosa. Proteomics analysis revealed significantly different proteins expressed following PAC treatment. In addition, we found that PACs potentiated the antibiotic activity of gentamicin in an in vivo model of infection using G. mellonella.
Results suggest that A-type proanthocyanidins may be a useful therapeutic against the biofilm-mediated infections caused by P. aeruginosa and should be further tested.
生物膜内的细菌在表型上对抗生素、干燥和宿主免疫系统更具抗性,使其成为许多微生物的重要毒力因子。蔓越莓汁长期以来一直用于预防尿路感染,而尿路感染通常与生物膜形成有关。最近的研究发现,蔓越莓中的A型原花青素具有抗大肠杆菌生物膜的特性。
我们使用结晶紫生物膜染色、刃天青代谢测定和共聚焦成像,研究了A型原花青素(PACs)破坏铜绿假单胞菌生物膜形成的能力。我们使用质谱分析PAC处理的蛋白质组学效应。我们还进行了协同试验以及体外和体内感染试验,以确定PACs单独使用或与庆大霉素联合使用是否有助于杀死铜绿假单胞菌以及细胞系和黄粉虫的存活。
蔓越莓PACs降低了铜绿假单胞菌的群游运动性。蔓越莓PACs显著破坏了铜绿假单胞菌的生物膜形成。蛋白质组学分析显示,PAC处理后表达的蛋白质有显著差异。此外,我们发现PACs在使用黄粉虫的体内感染模型中增强了庆大霉素的抗生素活性。
结果表明,A型原花青素可能是一种有效的治疗方法,用于对抗由铜绿假单胞菌引起的生物膜介导的感染,应进一步进行测试。