Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model

Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model
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DOI:
10.1099/mic.0.2007/006122-0
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发表时间:
2007-07-01
期刊:
影响因子:
2.8
通讯作者:
Bjarnsholt, Thomas
Bjarnsholt, Thomas
中科院分区:
生物学4区
文献类型:
--
作者:
Christensen, Louise D.;Moser, Claus;Bjarnsholt, Thomas

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铜绿假单胞菌是一种机会性人类病原体,可引起宿主生物体的慢性生物膜感染。铜绿假单胞菌利用群体感应(OS)来控制其毒力的表达,并建立和维持慢性感染。在这样的条件下,生物膜生长模式显著有助于铜绿假单胞菌对先天和适应性防御系统和许多抗生素的作用的耐受性。在本研究中,在小鼠腹腔内建立体内异物感染模型。实验数据表明,与野生型对应物相比,QS缺陷型铜绿假单胞菌更快地从硅胶植入体中清除。同时,与安慰剂治疗组相比,用QS抑制剂呋喃酮C-30治疗携带野生型铜绿假单胞菌定殖的植入物的小鼠导致植入物的清除显著更快。这些结果是用近交(BALB/c)和远交(NMRI)小鼠品系获得的。本研究结果支持了一种模型,通过该模型,功能性QS系统在细菌抵抗先天免疫系统清除的能力中发挥关键作用,并强烈表明,当用诱导QS缺乏的QS药物处理细菌时,小鼠对生物膜形成铜绿假单胞菌的先天防御效率得到改善。
Pseudomonas aeruginosa is an opportunistic human pathogen that causes chronic biofilm-based infections in host organisms. P. aeruginosa employs quorum sensing (OS) to control expression of its virulence, and to establish and maintain chronic infections. Under such conditions, the biofilm mode of growth contributes significantly to P. aeruginosa tolerance to the action of the innate and adaptive defence system and numerous antibiotics. In the present study, an in vivo foreign-body infection model was established in the peritoneal cavity of mice. Experimental data showed that QS-deficient P. aeruginosa are cleared more rapidly from silicone implants as compared to their wild-type counterparts. Concurrently, treatment with the QS inhibitor furanone C-30 of mice harbouring implants colonized with the wild-type P. aeruginosa resulted in a significantly faster clearing of the implants as compared to the placebo-treated group. These results were obtained with both an inbred (BALB/c) and an outbred (NMRI) mouse strain. The present results support a model by which functional QS systems play a pivotal role in the ability of bacteria to resist clearing by the innate immune system and strongly suggest that the efficiency of the mouse innate defence against biofilm-forming P. aeruginosa is improved when the bacteria are treated with QS drugs that induce QS deficiency.