Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopentylamides.
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 microM, 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.
Ishida
Takenori
T
Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8530, Japan.
Ikeda
Tsukasa
T
Takiguchi
Noboru
N
Kuroda
Akio
A
Ohtake
Hisao
H
Kato
Junichi
J
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D000222:Adaptation, Physiological / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology*; D017930:Genes, Reporter; D006017:Glycolipids / Q000037:antagonists & inhibitors; D006714:Homoserine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D011710:Pyocyanine / Q000037:antagonists & inhibitors; D053038:Quorum Sensing / Q000187:drug effects*; D037521:Virulence Factors / Q000037:antagonists & inhibitors; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000900:Anti-Bacterial Agents; D003517:Cyclopentanes; D006017:Glycolipids; C109860:N-(3-oxododecanoyl)homoserine lactone; C092312:N-butyrylhomoserine lactone; C523755:N-decanoyl cyclopentylamide; D037521:Virulence Factors; C418382:rhamnolipid; D006714:Homoserine; D011710:Pyocyanine; D001616:beta-Galactosidase; D010196:Pancreatic Elastase; D015107:4-Butyrolactone