Background. The opportunistic pathogen Pseudomonas aeruginosa is a major factor in the morbidity and mortality of cystic fibrosis (CF) sufferers. It causes chronic infections in the lungs of these patients that can last decades. P. aeruginosa is widespread in the environment, providing a reservoir for infection of individuals with CF. Currently, there is an incomplete understanding of how P. aeruginosa evolves to survive the hostile environment of the lung. To this end, we have collected isolates of P. aeruginosa from the lungs of a CF patient in 1991, and isolates from the same patient 21 years later. Aiming to further understand the processes involved in developing chronic infections.
Methods. The isolates were characterised using a combination of whole genome sequencing, RNA-seq, and phenotypic approaches.
Results. Whole genome sequence analysis indicates the modern isolates are derived from those obtained in 1991. Several hundred non-synonymous mutations separate the modern sequences from the ancestral sequences. Many mutations identified are in genes with unknown function. Also present are large deletions, bacteriophage acquisition, and significant differences in gene expression. Phenotypic differences between ancestral and modern isolates are consistent with the mutations and regulatory changes that have occurred in the 21-year infection. These include, changes in growth dynamics, motility, biofilm production, and antibiotic resistance, with most modern isolates being multi-drug resistant.
Conclusions. This research provides detailed insight into adaptation of P. aeruginosa to the CF lung environment over 21-years. A complete understanding of the evolution of these bacteria during infection may suggest novel strategies for treating infections.