Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
PLoS Pathog. 2013;9(8):e1003526. doi: 10.1371/journal.ppat.1003526. Epub 2013 Aug 8.
Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive "non-producing" cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.
生物膜内的细菌分泌并包围自身的细胞外基质，它是抵御抗生素攻击的第一道防线。多糖是生物膜基质的主要成分，参与表面黏附和生物膜的组织，但它们对生物膜耐药性的贡献在很大程度上仍不清楚。我们使用静态和连续流动生物膜实验相结合的方法表明，在生物膜发育的早期阶段，铜绿假单胞菌生物膜基质中的主要多糖之一 Psl 为具有不同生化特性的抗生素提供了通用的第一道防线。此外，我们通过混合菌株实验表明，缺乏 Psl 的抗生素敏感“非产生”细胞可以通过整合到含有 Psl 的生物膜中来获得耐药性。然而，非生产者会降低基质的保护能力，因此，过度整合可能导致整个群落的耐药性崩溃。我们的数据还表明，Psl 介导的保护可扩展到共培养生物膜中的大肠杆菌和金黄色葡萄球菌。总之，我们的研究表明，在生物膜发育的早期阶段，Psl 是生物膜群落对抗生素攻击的关键第一道障碍。
