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寡聚G CF-5/20对鼠肺感染模型中黏液型铜绿假单胞菌生物膜的破坏作用

OligoG CF-5/20 Disruption of Mucoid Pseudomonas aeruginosa Biofilm in a Murine Lung Infection Model.

作者信息

Hengzhuang Wang, Song Zhijun, Ciofu Oana, Onsøyen Edvar, Rye Philip D, Høiby Niels

机构信息

Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Denmark Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen, Denmark

Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Denmark.

出版信息

Antimicrob Agents Chemother. 2016 Apr 22;60(5):2620-6. doi: 10.1128/AAC.01721-15. Print 2016 May.

Abstract

Biofilm growth is a universal survival strategy for bacteria, providing an effective and resilient approach for survival in an otherwise hostile environment. In the context of an infection, a biofilm provides resistance and tolerance to host immune defenses and antibiotics, allowing the biofilm population to survive and thrive under conditions that would destroy their planktonic counterparts. Therefore, the disruption of the biofilm is a key step in eradicating persistent bacterial infections, as seen in many types of chronic disease. In these studies, we used both in vitro minimum biofilm eradication concentration (MBEC) assays and an in vivo model of chronic biofilm infection to demonstrate the biofilm-disrupting effects of an alginate oligomer, OligoG CF-5/20. Biofilm infections were established in mice by tracheal instillation of a mucoid clinical isolate of Pseudomonas aeruginosa embedded in alginate polymer beads. The disruption of the biofilm by OligoG CF-5/20 was observed in a dose-dependent manner over 24 h, with up to a 2.5-log reduction in CFU in the infected mouse lungs. Furthermore, in vitro assays showed that 5% OligoG CF-5/20 significantly reduced the MBEC for colistin from 512 μg/ml to 4 μg/ml after 8 h. These findings support the potential for OligoG CF-5/20 as a biofilm disruption agent which may have clinical value in reducing the microbial burden in chronic biofilm infections.

摘要

生物膜生长是细菌普遍采用的生存策略,为细菌在原本恶劣的环境中生存提供了一种有效且坚韧的方式。在感染的情况下,生物膜对宿主免疫防御和抗生素具有抗性和耐受性,使生物膜群体能够在会破坏其浮游同类的条件下存活并繁衍。因此,破坏生物膜是根除持续性细菌感染的关键步骤,这在许多类型的慢性疾病中都有体现。在这些研究中,我们使用了体外最小生物膜清除浓度(MBEC)测定法和慢性生物膜感染的体内模型,以证明藻酸盐寡聚物OligoG CF-5/20的生物膜破坏作用。通过气管内注入包埋在藻酸盐聚合物珠中的黏液型铜绿假单胞菌临床分离株,在小鼠体内建立生物膜感染。在24小时内观察到OligoG CF-5/20对生物膜的破坏呈剂量依赖性,感染小鼠肺部的CFU最多减少2.5个对数。此外,体外试验表明,5%的OligoG CF-5/20在8小时后可将黏菌素的MBEC从512μg/ml显著降低至4μg/ml。这些发现支持了OligoG CF-5/20作为生物膜破坏剂的潜力,其可能在降低慢性生物膜感染中的微生物负荷方面具有临床价值。

相似文献

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In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa.抗菌药物对产生物膜铜绿假单胞菌的体内疗效
Antimicrob Agents Chemother. 2015 Aug;59(8):4974-81. doi: 10.1128/AAC.00194-15. Epub 2015 Jun 8.

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