Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate.
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.
Kobayashi
Takao
T
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. ktakao@idac.tohoki.ac.jp
Tateda
Kazuhiro
K
Matsumoto
Tetsuya
T
Miyazaki
Shuichi
S
Watanabe
Akira
A
Nukiwa
Toshihiro
T
Yamaguchi
Keizo
K
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
D000900:Anti-Bacterial Agents; D018942:Macrolides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D010196:Pancreatic Elastase