title: A low concentration of azithromycin inhibits the mRNA expression of N-acyl homoserine lactone synthesis enzymes, upstream of lasI or rhlI, in Pseudomonas aeruginosa.
abstract: Low-dose macrolides are effective therapy in patients with chronic lung infections, but the mechanisms of action are unclear. In this study, we performed DNA microarray analysis of Pseudomonas aeruginosa after treatment with a low concentration of azithromycin. We found that a sub-MIC of azithromycin didn't change mRNA expression of quorum-sensing related genes (lasI, lasR, rhlI, rhlR, vft, rsaL), but lowered expression of most N-acyl homoserine lactone (AHL) synthesis enzymes upstream of lasI and rhlI. We propose that small down regulation of these enzymes cumulatively resulted in a larger decrease of AHL production and inhibition of quorum-sensing in P. aeruginosa.
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-Ku, Osaka 554-0022, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D054742:Acyl-Butyrolactones / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D046228:Microarray Analysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D012329:RNA, Bacterial / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054742:Acyl-Butyrolactones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C081237:LasI protein, Pseudomonas aeruginosa; D012329:RNA, Bacterial; D012333:RNA, Messenger; D017963:Azithromycin