A low concentration of azithromycin inhibits the mRNA expression of N-acyl homoserine lactone synthesis enzymes, upstream of lasI or rhlI, in Pseudomonas aeruginosa.
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.
Kai
Toshihiro
T
Dainippon Sumitomo Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-Ku, Osaka 554-0022, Japan.
Tateda
Kazuhiro
K
Kimura
Soichiro
S
Ishii
Yoshikazu
Y
Ito
Hideaki
H
Yoshida
Hiroaki
H
Kimura
Toru
T
Yamaguchi
Keizo
K
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
D054742:Acyl-Butyrolactones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C081237:LasI protein, Pseudomonas aeruginosa; D012329:RNA, Bacterial; D012333:RNA, Messenger; D017963:Azithromycin