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