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- Title
Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate.
- Authors
Kobayashi, Takao; Tateda, Kazuhiro; Matsumoto, Tetsuya; Miyazaki, Shuichi; Watanabe, Akira; Nukiwa, Toshihiro; Yamaguchi, Keizo
- Abstract
<bold>Objective: </bold>Accumulating data have demonstrated that macrolide antibiotics suppress Pseudomonas aeruginosa virulence, which may explain the efficacy of macrolides in clinical settings. We examined the virulence of macrolide-treated bacteria in vivo.<bold>Methods: </bold>P. aeruginosa PAO-1 was grown for 24 h on agar containing sub-MIC antibiotics, and then mice were challenged intranasally with 10(7) cfu of bacteria.<bold>Results and Conclusions: </bold>The mortality rate of mice inoculated with bacteria grown in the presence of clarithromycin (10 mg/L), erythromycin (10 mg/L) or azithromycin (5 mg/L) was 80%, 80% and 100%, respectively. In contrast, none of the mice inoculated with non-treated bacteria or bacteria treated with other antibiotics died. Lung weight and protein concentration in bronchoalveolar lavage fluid (BALF) were significantly higher in the clarithromycin group between 3 and 9 h. Moreover, we detected higher levels of tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in the BALF of these mice. These data demonstrate that macrolide-treated P. aeruginosa induced paradoxically strong responses, such as elevation of TNF-alpha, NO and permeability in the lungs.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2002, Vol 50, Issue 1, p59
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkf048