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群体感应信号表明囊性纤维化患者的肺部受到细菌生物膜的感染。

Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms.

作者信息

Singh P K, Schaefer A L, Parsek M R, Moninger T O, Welsh M J, Greenberg E P

机构信息

Howard Hughes Medical Institute & Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.

出版信息

Nature. 2000 Oct 12;407(6805):762-4. doi: 10.1038/35037627.

Abstract

The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment. This suggests that P. aeruginosa might exist as biofilms--structured communities of bacteria encased in a self-produced polymeric matrix--in the cystic fibrosis lung. Consistent with this hypothesis, microscopy of cystic fibrosis sputum shows that P. aeruginosa are in biofilm-like structures. P. aeruginosa uses extracellular quorum-sensing signals (extracellular chemical signals that cue cell-density-dependent gene expression) to coordinate biofilm formation. Here we found that cystic fibrosis sputum produces the two principal P. aeruginosa quorum-sensing signals; however, the relative abundance of these signals was opposite to that of the standard P. aeruginosa strain PAO1 in laboratory broth culture. When P. aeruginosa sputum isolates were grown in broth, some showed quorum-sensing signal ratios like those of the laboratory strain. When we grew these isolates and PAO1 in a laboratory biofilm model, the signal ratios were like those in cystic fibrosis sputum. Our data support the hypothesis that P. aeruginosa are in a biofilm in cystic fibrosis sputum. Moreover, quorum-sensing signal profiling of specific P. aeruginosa strains may serve as a biomarker in screens to identify agents that interfere with biofilm development.

摘要

尽管进行了积极的抗生素治疗,铜绿假单胞菌仍会永久性地定植于囊性纤维化患者的肺部。这表明在囊性纤维化患者的肺部,铜绿假单胞菌可能以生物膜的形式存在,生物膜是一种由细菌构成的结构化群落,被包裹在自身产生的聚合基质中。与这一假设相符的是,对囊性纤维化患者痰液进行显微镜检查发现,铜绿假单胞菌呈生物膜样结构。铜绿假单胞菌利用细胞外群体感应信号(即能提示细胞密度依赖性基因表达的细胞外化学信号)来协调生物膜的形成。我们发现,囊性纤维化患者的痰液能产生铜绿假单胞菌的两种主要群体感应信号;然而,这些信号的相对丰度与实验室肉汤培养中的标准铜绿假单胞菌菌株PAO1相反。当在肉汤中培养铜绿假单胞菌痰液分离株时,一些分离株显示出与实验室菌株相似的群体感应信号比例。当我们在实验室生物膜模型中培养这些分离株和PAO1时,信号比例与囊性纤维化患者痰液中的相似。我们的数据支持了以下假设:在囊性纤维化患者的痰液中,铜绿假单胞菌以生物膜的形式存在。此外,特定铜绿假单胞菌菌株的群体感应信号分析可能作为一种生物标志物,用于筛选干扰生物膜形成的药物。

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