Time-resolved dual transcriptomics of Pseudomonas aeruginosa biofilm formation in cystic fibrosis

Abstract

Pseudomonas aeruginosa biofilms cause severe infections in the airways of patients suffering from cystic fibrosis (CF) that are difficult to eradicate, even with intensive antibiotic therapy. The main goal of this study was to define the dual transcriptional response associated with the formation of P. aeruginosa biofilms in a polarized lung epithelium monolayer. We analyzed the dual response of healthy and CF epithelium after infection with P. aeruginosa isolates from acute and chronic infections. Our results show that strains of P. aeruginosa isolated from chronic infections specifically increase the expression of secretion systems of type I, III and VI to hijack the host response. Conversely, strains associated with acute illness use ABC transporters to counteract the antimicrobial response. In return, a distinctive expression pattern in the CF epithelium, including a high degree of cytokine secretion and keratinization, is largely observed in acute infections. Our results show that both host and pathogen genomic backgrounds contribute to the outcome of infection and specific transcriptional signatures could be used in the diagnosis, particularly in CF patients.