Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins
Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins
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DOI：
10.1038/mi.2011.27
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发表时间：
2011-11-01
影响因子：
8
通讯作者：
Bakaletz, L. O.
中科院分区：
文献类型：
--
作者：
Goodman, S. D.;Obergfell, K. P.;Bakaletz, L. O.
导致慢性和/或复发性疾病的细菌通常依赖于生物膜生活方式。生物膜结构的基础是细胞外聚合物（EPS），其充当免疫系统效应物和抗微生物剂的屏障。最近的工作突出了细胞外DNA（eDNA）作为许多致病性生物膜共同的关键组分。在这里，我们表明，DNABII家族的蛋白质，众所周知，其强大的结构影响细胞内DNA，也是至关重要的EPS基质的完整性，包含eDNA的生物膜。事实上，针对纯化的大肠杆菌DNABII家族成员衍生的抗血清在体外快速破坏由多种人类病原体形成的生物膜EPS。此外，当该蛋白质家族的成员在其中细菌已经在感染部位形成稳健的生物膜的动物模型中用作免疫原时，所产生的靶向免疫应答强烈地改善了体内的这种生物膜疾病。最后，这种方法来减少生物膜的EPS显示协同工作，否则无效的传统抗微生物方法在体外。我们讨论了靶向DNABII家族成员作为治疗生物膜疾病的潜在通用策略的前景。
Bacteria that cause chronic and/or recurrent diseases often rely on a biofilm lifestyle. The foundation of the biofilm structure is the extracellular polymeric substance (EPS) that acts as a barrier to both effectors of the immune system and antimicrobial agents. Recent work has highlighted extracellular DNA (eDNA) as a key component common to many pathogenic biofilms. Here, we show that the DNABII family of proteins, well known for their strong structural influences on intracellular DNA, was also critical for the integrity of the EPS matrix of biofilms that contain eDNA. In fact, antisera derived against a purified Escherichia coli DNABII family member rapidly disrupts the biofilm EPS formed by multiple human pathogens in vitro. In addition, when a member of this family of proteins was used as an immunogen in an animal model in which the bacteria had already formed a robust biofilm at the site of infection, the resultant targeted immune response strongly ameliorated this biofilm disease in vivo. Finally, this methodology to debulk the biofilm of EPS was shown to work synergistically with otherwise ineffective traditional anti-microbial approaches in vitro. We discuss the prospects for targeting DNABII family members as a potential universal strategy for treating biofilm diseases.