Yu Shan, Su Tiantian, Wu Huijun, Liu Shiheng, Wang Di, Zhao Tianhu, Jin Zengjun, Du Wenbin, Zhu Mei-Jun, Chua Song Lin, Yang Liang, Zhu Deyu, Gu Lichuan, Ma Luyan Z
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
University of the Chinese Academy of Sciences, Beijing 100049, China.
Cell Res. 2015 Dec;25(12):1352-67. doi: 10.1038/cr.2015.129. Epub 2015 Nov 27.
Biofilms are surface-associated communities of microorganism embedded in extracellular matrix. Exopolysaccharide is a critical component in the extracellular matrix that maintains biofilm architecture and protects resident biofilm bacteria from antimicrobials and host immune attack. However, self-produced factors that target the matrix exopolysaccharides, are still poorly understood. Here, we show that PslG, a protein involved in the synthesis of a key biofilm matrix exopolysaccharide Psl in Pseudomonas aeruginosa, prevents biofilm formation and disassembles existing biofilms within minutes at nanomolar concentrations when supplied exogenously. The crystal structure of PslG indicates the typical features of an endoglycosidase. PslG mainly disrupts the Psl matrix to disperse bacteria from biofilms. PslG treatment markedly enhances biofilm sensitivity to antibiotics and macrophage cells, resulting in improved biofilm clearance in a mouse implant infection model. Furthermore, PslG shows biofilm inhibition and disassembly activity against a wide range of Pseudomonas species, indicating its great potential in combating biofilm-related complications.
生物膜是嵌入细胞外基质中的微生物表面相关群落。胞外多糖是细胞外基质中的关键成分,它维持生物膜结构,并保护生物膜内的常驻细菌免受抗菌剂和宿主免疫攻击。然而,针对基质胞外多糖的自身产生的因子仍知之甚少。在这里,我们表明,PslG是一种参与铜绿假单胞菌关键生物膜基质胞外多糖Psl合成的蛋白质,当外源提供时,它能在纳摩尔浓度下在几分钟内阻止生物膜形成并分解现有的生物膜。PslG的晶体结构表明其具有内切糖苷酶的典型特征。PslG主要破坏Psl基质以将细菌从生物膜中分散出来。PslG处理显著增强生物膜对抗生素和巨噬细胞的敏感性,从而在小鼠植入感染模型中改善生物膜清除。此外,PslG对多种假单胞菌属物种显示出生物膜抑制和分解活性,表明其在对抗生物膜相关并发症方面具有巨大潜力。