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A New Quorum-Sensing Inhibitor Attenuates Virulence and Decreases Antibiotic Resistance in Pseudomonas aeruginosa

Quorum sensing (QS) has been a novel target for the treatment of infectious diseases. Here structural analogs of Pseudomonas aeruginosa autoinducer N-acyl homoserine lactone (AHL) were investigated for QS inhibitor (QSI) activity and a novel QSI was discovered, N-decanoyl-L-homoserine benzyl ester (...

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Published in:The journal of microbiology 2012, 50(6), , pp.987-993
Main Authors: Yang, Yu-Xiang, Fudan University, Shanghai, P. R. China, Xu, Zhen-Hua, Fudan University, Shanghai, P. R. China, Zhang, Yu-Qian, Fudan University, Shanghai, P. R. China, Tian, Jing, Nanjing University of Posts and Telecommunications, Nanjing, Jiangsu, P. R. China, Weng, Li-Xing, Fudan University, Shanghai, P. R. China, Wang, Lian-Hui, Nanjing University of Posts and Telecommunications, Nanjing, Jiangsu, P. R. China
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Language:English
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Summary:Quorum sensing (QS) has been a novel target for the treatment of infectious diseases. Here structural analogs of Pseudomonas aeruginosa autoinducer N-acyl homoserine lactone (AHL) were investigated for QS inhibitor (QSI) activity and a novel QSI was discovered, N-decanoyl-L-homoserine benzyl ester (C2). Virulence assays showed that C2 downregulated total protease and elastase activities, as well as the production of rhamnolipid, that are controlled by QS in P. aeruginosa wild-type strain PAO1 without affecting growth. C2 was also shown to inhibit swarming motility of PAO1. Using a microdilution checkerboard method, we identified synergistic interactions between C2 and several antibiotics, tobramycin, gentamycin, cefepime, and meropenem. Data from real-time RT-PCR suggested that C2 inhibited the expression of lasR (29.67%), lasI (21.57%), rhlR (28.20%), and rhlI (29.03%).
ISSN:1225-8873
1976-3794
DOI:10.1007/s12275-012-2149-7