Effect of long-term, low-dose macrolide exposure on Pseudomonas aeruginosa in vitro

Abstract

Pseudomonas aeruginosa is a common cause of chronic respiratory tract infection in patients with pulmonary disorders such as diffuse panbronchiolitis (DPB). Long-term, low-dose macrolide treatment has been reported to significantly increase the survival rate of patients with DPB. However, macrolides do not exert any antibacterial effect on P. aeruginosa. Macrolides have been reported to inhibit P. aeruginosa virulence factors; however, in previous studies, the effects of macrolides on P. aeruginosa via short-term exposure were evaluated. Hence, in this study, we aimed to determine the effects of long-term, low-dose macrolide (erythromycin and clarithromycin) treatment on P. aeruginosa over 2 years in vitro. The virulence factors of P. aeruginosa (total proteolytic activity, elastase activity, and pyocyanin production) and cytotoxicity to the human lung epithelial adenocarcinoma cell line A549 treated with the supernatant of macrolide-exposed P. aeruginosa were analyzed. Long periods of macrolide exposure decreased P. aeruginosa virulence factors and A549 cell cytotoxicity. Long-term, low-dose macrolide treatment temporally reduced the pathogenicity of P. aeruginosa by decreasing its virulence factors. The present findings may help modify the clinical course of DPB.