Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections

Abstract

Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification.

Trends

During chronic lung infections of CF patients common genetic adaptations occur in P. aeruginosa, such as conversion to mucoidy, loss of virulence factors, and resistance to antibiotics.

Although pathoadaptive mutations in regulatory proteins are common, the actual regulators affected vary between populations.

P. aeruginosa populations in CF lungs exhibit high levels of phenotypic diversity.

Fine-scale population genomics approaches reveal that divergent sublineages can coexist, with evidence for regional isolation in the spatially structured and heterogeneous lung environment.

Experimental evolution is beginning to provide insights into the selective drivers of evolution in P. aeruginosa infection, including the role of social interactions.