Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate
Authors: Kobayashi, Takao1; Tateda, Kazuhiro1; Matsumoto, Tetsuya1; Miyazaki, Shuichi1; Watanabe, Akira2; Nukiwa, Toshihiro2; Yamaguchi, Keizo1
Source: Journal of Antimicrobial Chemotherapy, Volume 50, Number 1, July 2002 , pp. 59-66(8)
Publisher: Oxford University Press
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Abstract:
Objective: 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.Methods: P. aeruginosa PAO-1 was grown for 24 h on agar containing sub-MIC antibiotics, and then mice were challenged intranasally with 107 cfu of bacteria.Results and conclusions: 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-
(TNF-) 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-, NO and permeability in the lungs.
Document Type: Research article
Affiliations: 1: Department of Microbiology, Toho University School of Medicine, Tokyo; 2: Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
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