title: A new quorum-sensing inhibitor attenuates virulence and decreases antibiotic resistance in Pseudomonas aeruginosa.
abstract: 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 down-regulated 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%).
authors.affiliation: Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Yang
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Xu
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Li-Xing
authors.initials: LX
authors.lastname: Weng
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004357:Drug Synergism; D015964:Gene Expression Regulation, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology*; D053038:Quorum Sensing / Q000235:genetics; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C581696:N-decanoylhomoserine benzyl ester; D037521:Virulence Factors; D006714:Homoserine