gene expression changes during established biofilm infection in a cystic fibrosis lung model.

Abstract

The opportunistic pathogenforms biofilm infections in the lungs of people with the genetic condition cystic fibrosis (CF) that can persist for decades. There are numerouslifestyle changes associated with chronic biofilm infection that are cued by the CF lung environment. These include a loss of virulence, metabolic changes and increased antimicrobial tolerance. We have investigatedPA14 biofilm infection over 7 days in anpig lung (EVPL) model for CF, previously shown to facilitate formation of a clinically relevantbiofilm structure with expression of key genes comparable to human infection. We have comparedgene expression between sequential time points: 24 h, 48 h and 7 days post-infection, and investigated tolerance to polymyxins. Our results demonstrate that the EVPL model can maintain abiofilm population, which exhibits increased antibiotic tolerance, for at least 7 days. Differential expression of antimicrobial resistance-associated genes was not observed; however, there was significant upregulation of sulphur metabolism and maintenance of a structured biofilm. Our findings demonstrate that 7 days is a viable time point for studying established, chronic biofilm infection in the EVPL model and provide insight into the accompanying gene expression changes.