title: Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate.
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 10(7) cfu of bacteria.
  
  
  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-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.
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. ktakao@idac.tohoki.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018942:Macrolides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D010196:Pancreatic Elastase / Q000276:immunology / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D010196:Pancreatic Elastase