Iron salts perturb biofilm formation and disrupt existing biofilms of Pseudomonas aeruginosa
Iron salts perturb biofilm formation and disrupt existing biofilms of Pseudomonas aeruginosa
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DOI：
10.1016/j.chembiol.2005.05.007
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发表时间：
2005-07-01
影响因子：
--
通讯作者：
Hergenrother, PJ
中科院分区：
文献类型：
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作者：
Musk, DJ;Banko, DA;Hergenrother, PJ
细菌生物膜被认为有助于人类各种难治性感染的存活。具体而言，铜绿假单胞菌中的生物膜产生已被证明在囊性纤维化（CF）患者的慢性感染中起重要作用。不幸的是，没有临床上有效的生物膜形成抑制剂可用。在384孔板中对铜绿假单胞菌PA 14中非抗生素生物膜抑制剂的4509种化合物进行快速筛选。在这些化合物中，柠檬酸铁铵以剂量依赖性方式抑制生物膜形成;其他铁盐的功能相似。除了静态培养中的生物膜抑制外，在流动室实验中，通过切换到富铁培养基可以破坏和清除预生长的生物膜。此外，从20名CF患者的痰中提取的铜绿假单胞菌菌株对铁水平升高表现出类似的反应。以前的表达谱分析表明，高水平的铁抑制基因的表达，其产品是必不可少的清除铁和这些基因的表达是至关重要的毒力。我们的研究结果，结合现有的转录谱数据，现在表明，铁浓度升高抑制某些基因的表达，这些基因对铜绿假单胞菌生物膜的产生至关重要。
Bacterial biofilms are thought to aid in the survivability of a variety of intractable infections in humans. Specifically, biofilm production in Pseudomonas aeruginosa has been shown to play a significant role in chronic infection of cystic fibrosis (CF) patients. Unfortunately, no clinically effective inhibitors of biofilm formation are available. A rapid screen of 4509 compounds for nonantibiotic biofilm inhibitors in Pseudomonas aeruginosa PA14 was executed in 384-well plates. Among those compounds, ferric ammonium citrate inhibited biofilm formation in a dose-dependent manner; other iron salts functioned similarly. In addition to biofilm inhibition in static culture, pre-grown biofilms could be disrupted and cleared by switching to iron-rich media in flow-chamber experiments. Furthermore, P. aeruginosa strains taken from the sputum of 20 CF patients showed a similar response to elevated iron levels. Previous expression-profiling analyses demonstrated that high levels of iron repress the expression of genes whose products are essential for scavenging iron and that expression of these genes is critical for virulence. Our results, combined with existing transcriptional-profiling data, now indicate that elevated iron concentrations repress the expression of certain genes essential for biofilm production in P. aeruginosa.