Rapid diversification ofPseudomonas aeruginosain cystic fibrosis lung-like conditions

Abstract

Chronic infection of the cystic fibrosis (CF) airway by the opportunistic pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality for adult CF patients. Prolonged infections are accompanied by adaptation of P. aeruginosa to the unique conditions of the CF lung environment, as well as marked diversification of the pathogen into phenotypically and genetically distinct strains that can coexist for years within a patient. Little is known, however, about the causes of this diversification and its impact on patient health. Here, we show experimentally that, consistent with ecological theory of diversification, the nutritional conditions of the CF airway can cause rapid and extensive diversification of P. aeruginosa. Mucin, the substance responsible for the increased viscosity associated with the thick mucus layer in the CF airway, had little impact on within-population diversification but did promote divergence among populations. Furthermore, in vitro evolution recapitulated traits thought to be hallmarks of chronic infection, including reduced motility and increased biofilm formation, and the range of phenotypes observed in a collection of clinical isolates. Our results suggest that nutritional complexity and reduced dispersal can drive evolutionary diversification of P. aeruginosa independent of other features of the CF lung such as an active immune system or the presence of competing microbial species. We suggest that diversification, by generating extensive phenotypic and genetic variation on which selection can act, may be a key first step in the development of chronic infections.

Evolutionary Genomics of Niche-Specific Adaptation to the Cystic Fibrosis Lung in Pseudomonas aeruginosa

“…The complex, amino acid-rich, nutritional conditions of the CF lung are thought to provide ample opportunity for resource specialization ( La Rosa et al. 2018 ) and adaptive diversification ( Schick and Kassen 2018 ). Consistent with this hypothesis, key regulators of preferential carbon source utilization ( Sonnleitner et al.…”

Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors

“…P. aeruginosa elicits a robust acute host inflammatory response; however, it manages to persist within the airways [ 1 ]. Its tremendous metabolic flexibility allows it to readily adapt to airway conditions, which has been widely studied in people with CF where P. aeruginosa chronic infection is the leading cause of lung function decline [ 214 ]. CF is the most common autosomal recessive genetic disorder among Caucasians.…”

Adapting to the Airways: Metabolic Requirements of Pseudomonas aeruginosa during the Infection of Cystic Fibrosis Patients

“…Even though mucins are an available source of both carbon and nitrogen in the mucus, P. aeruginosa is unable to catabolize this nutrient [24]. However, while mucins may not directly contribute to growth of P. aeruginosa in the CF lungs, they do promote diversification in lung-like conditions underlining the role of nutritional and structural complexity in driving evolution [25]. Pulmonary surfactants, which consist of a mixture of lipids and proteins secreted by the epithelial cells, play a crucial role in reducing the surface tension at the air/liquid interface in the lungs, which helps to avoid alveolar collapse at the end of expiration and to ease the breathing [26].…”