Suppression of Pseudomonas aeruginosa quorum-sensing systems by macrolides: a promising strategy or an oriental mystery? |
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Authors: | Kazuhiro Tateda Yoshikazu Ishii Soichiro Kimura Manabu Horikawa Shinichi Miyairi Keizo Yamaguchi |
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Institution: | (1) Department of Microbiology and Infectious Disease, Toho University School of Medicine, 5-21-16 Ohmorinishi, Ohtaku, Tokyo 143-8540, Japan;(2) Suntory Institute for Bioorganic Research, Osaka, Japan;(3) Laboratory of Bio-organic Chemistry, College of Pharmacy, Nihon University, Chiba, Japan |
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Abstract: | A breakthrough in antibiotic chemotherapy for patients with chronic Pseudomonas aeruginosa pulmonary infections was brought about by findings in a patient with diffuse panbronchiolitis (DPB), who had been treated
with erythromycin over a period of years. Recent clinical trials have demonstrated that long-term macrolide therapy can be
used not only for DPB patients but also for those with other chronic infections, including patients with cystic fibrosis (CF).
The pathogenesis of chronic P. aeruginosa infection is considered to arise from a bacterial cell-to-cell signaling mechanism, named “quorum-sensing”, which enables
the bacteria to coordinately turn on and off their virulence genes through the production of autoinducer molecules. Accumulating
evidence from clinical and basic science fields suggests the potential of macrolides as Pseudomonas quorum-sensing inhibitors. In this review, we briefly summarize the data on the clinical efficacy of macrolides in DPB and
CF patients. Then we discuss the mechanisms of action of macrolides from the viewpoint of sub-minimum inhibitory concentration
(sub-MIC) macrolide effects on P. aeruginosa, particularly the potential activity of this antibiotic to suppress the bacterial quorum-sensing system. |
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Keywords: | Quorum-sensing system Macrolide Pseudomonas aeruginosa Autoinducer Diffuse panbronchiolitis Cystic fibrosis |
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