Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate

Takao Kobayashi, Kazuhiro Tateda, Tetsuya Matsumoto, Shuichi Miyazaki, Akira Watanabe, Toshihiro Nukiwa, Keizo Yamaguchi

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    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 factors-α (TNF-α) 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-α, NO and permeability in the lungs.

    Original languageEnglish
    Pages (from-to)59-66
    Number of pages8
    JournalJournal of Antimicrobial Chemotherapy
    Volume50
    Issue number1
    DOIs
    Publication statusPublished - 2002

    ASJC Scopus subject areas

    • Pharmacology
    • Microbiology (medical)
    • Infectious Diseases
    • Pharmacology (medical)

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