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: Toshihiro Kai, Kazuhiro Tateda, Soichiro Kimura, Yoshikazu Ishii, Hideaki Ito, Hiroaki Yoshida, Toru Kimura, Keizo Yamaguchi
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 22 Issue 6 Pg. 483-6 (Dec 2009) ISSN: 1522-9629 [Electronic] England
• PMID: 19393329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acyl-Butyrolactones
• Anti-Bacterial Agents
• Bacterial Proteins
• LasI protein, Pseudomonas aeruginosa
• RNA, Bacterial
• RNA, Messenger
• Azithromycin

Topics

• Acyl-Butyrolactones (metabolism)
• Anti-Bacterial Agents (pharmacology)
• Azithromycin (pharmacology)
• Bacterial Proteins (biosynthesis, genetics)
• Microarray Analysis
• Pseudomonas aeruginosa (drug effects, genetics, metabolism)
• RNA, Bacterial (biosynthesis)
• RNA, Messenger (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)