PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix

PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix
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PslG 是一种自产糖基水解酶,通过破坏胞外多糖基质来引发生物膜分解。

DOI:
10.1038/cr.2015.129
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发表时间:
2015-12-01
期刊:
影响因子:
44.1
通讯作者:
Ma, Luyan Z.
Ma, Luyan Z.
中科院分区:
生物学1区
文献类型:
--
作者:
Yu, Shan;Su, Tiantian;Ma, Luyan Z.

文献摘要

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生物膜是嵌入在细胞外基质中的表面相关微生物群落。胞外多糖是细胞外基质中的关键成分,它维持生物膜的结构,保护驻留的生物膜细菌免受抗菌剂和宿主免疫的攻击。然而,以基质胞外多糖为靶点的自身产生的因子仍然知之甚少。在这里,我们证明了PSLG,一种参与铜绿假单胞菌中关键生物膜基质胞外多糖PSL合成的蛋白质,当从外部供应时,可以防止生物膜的形成,并在几分钟内以纳摩尔浓度分解现有的生物膜。PSLG的晶体结构显示了典型的内切糖苷酶的特征。PSLG主要破坏PSL基质,从生物膜中分散细菌。PSLG治疗显著增强了生物膜对抗生素和巨噬细胞的敏感性,从而改善了小鼠植入物感染模型中的生物膜清除。此外,PSLG对多种假单胞菌具有生物被膜抑制和分解活性,表明其在对抗生物被膜相关并发症方面具有巨大的潜力。
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.