Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1:: a global approach
Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1:: a global approach
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DOI：
10.1128/aac.50.5.1680-1688.2006
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Hussler, S
中科院分区：
文献类型：
--
作者：
Nalca, Y;Jänsch, L;Hussler, S
据报道，大环内酯类药物如阿奇霉素对囊性纤维化患者的慢性肺部感染有益。尽管作用机制尚不清楚，但已表明抗炎作用以及大环内酯类对铜绿假单胞菌毒力因子产生的干扰有助于改善临床结局。在这项研究中，我们使用了一种系统的方法，并分析了阿奇霉素对铜绿假单胞菌PAO1培养物与未经处理的对照物的总体转录模式和蛋白质表达谱的影响。本研究最显著的结果是发现阿奇霉素具有广泛的群体感应拮抗活性。根据群体感应系统的抑制，毒力因子的生产减少，氧化应激反应受损，而III型分泌系统强烈诱导。此外，铜绿假单胞菌运动性降低，这可能是先前观察到的阿奇霉素处理的培养物的生物膜形成能力受损的原因。阿奇霉素对铜绿假单胞菌中群体感应依赖性毒力因子产生、生物膜形成和氧化应激抗性的干扰为囊性纤维化的大环内酯类药物治疗带来了巨大的希望。显然，在慢性铜绿假单胞菌感染的管理中，应更多地关注群体感应拮抗剂大环内酯类药物，作为群体感应拮抗剂，大环内酯类药物可能在更广泛的应用中获得至关重要的作用。
The administration of macrolides such as azithromycin for chronic pulmonary infection of cystic fibrosis patients has been reported to be of benefit. Although the mechanisms of action remain obscure, anti-inflammatory effects as well as interference of the macrolide with Pseudomonas aeruginosa virulence factor production have been suggested to contribute to an improved clinical outcome. In this study we used a systematic approach and analyzed the impact of azithromycin on the global transcriptional pattern and the protein expression profile of P. aeruginosa PAO1 cultures versus those in untreated controls. The most remarkable result of this study is the finding that azithromycin exhibited extensive quorum-sensing antagonistic activities. In accordance with the inhibition of the quorum-sensing systems, virulence factor production was diminished and the oxidative stress response was impaired, whereas the type III secretion system was strongly induced. Moreover, P. aeruginosa motility was reduced, which probably accounts for the previously observed impaired biofilm formation capabilities of azithromycin-treated cultures. The interference of azithromycin with quorum-sensing-dependent virulence factor production, biofilm formation, and oxidative stress resistance in P. aeruginosa holds great promise for macrolide therapy in cystic fibrosis. Clearly quorum-sensing antagonist macrolides should be paid more attention in the management of chronic A aeruginosa infections, and as quorum-sensing antagonists, macrolides might gain vital importance for more general application against chronic infections.