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Appl. Environ. Microbiol. doi:10.1128/AEM.02233-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Inhibition of Quorum Sensing in Pseudomonas aeruginosa by N-Acyl Cyclopentylamides

Takenori Ishida, Tsukasa Ikeda, Noboru Takiguchi, Akio Kuroda, Hisao Ohtake, and Junichi Kato*

Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8530, Department of Applied Chemistry, Utsunomiya University, Utsunomiya, Tochigi 321-8585, Department of Biotechnology, Osaka University, Suita, Osaka 565-0871, Japan

* To whom correspondence should be addressed. Email: jun{at}hiroshima-u.ac.jp.


   Abstract

N-Octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhlA-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-Decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor and its concentrations required for half-maximal inhibition for lasB-lacZ and rhlA-lacZ expression were 80 and 90 µM, respectively. C10-CPA also inhibited production of virulence factors including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-L-homoserine lactone (PAI1) and rhlA-lacZ by N-butanoyl-L-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum sensing systems via inhibiting interaction between their response regulators (LasR and RhlR) and autoinducers.




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