Abstract
BackgroundDuring chronic lung infections of cystic fibrosis patients Pseudomonas aeruginosa populations undergo extensive evolutionary diversification. However, the selective drivers of this evolutionary process are poorly understood. To test the effects of temperate phages on diversification in P. aeruginosa biofilms we experimentally evolved populations of P. aeruginosa for approximately 240 generations in artificial sputum medium with or without a community of three temperate phages.ResultsAnalysis of end-point populations using a suite of phenotypic tests revealed extensive phenotypic diversification within populations, but no significant differences between the populations evolved with or without phages. The most common phenotypic variant observed was loss of all three types of motility (swimming, swarming and twitching) and resistance to all three phages. Despite the absence of selective pressure, some members of the population evolved antibiotic resistance. The frequency of antibiotic resistant isolates varied according to population and the antibiotic tested. However, resistance to ceftazidime and tazobactam-piperacillin was observed more frequently than resistance to other antibiotics, and was associated with higher prevelence of isolates exhibiting a hypermutable phenotype and increased beta-lactamase production.ConclusionsWe observed considerable within-population phenotypic diversity in P. aeruginosa populations evolving in the artificial sputum medium biofilm model. Replicate populations evolved both in the presence and absence of phages converged upon similar sets of phenotypes. The evolved phenotypes, including antimicrobial resistance, were similar to those observed amongst clinical isolates from cystic fibrosis infections.
Highlights
During chronic lung infections of cystic fibrosis patients Pseudomonas aeruginosa populations undergo extensive evolutionary diversification
Temperate phages are abundant in the cystic fibrosis (CF) lung [25], and we have demonstrated previously that Liverpool Epidemic Strain (LES) temperate phages can both mediate and drive adaptive evolution during experimental evolution in a biofilm model system, by increasing the supply of mutations in genes involved in type IV pilin biogenesis and quorum sensing through insertional inactivation of bacterial genes [26, 27])
Analysis of molecular variance (AMOVA) indicated that the majority of the phenotypic variance was associated with diversity within (74%) and between populations (24%), whereas less than 2% of the variation was explained by treatment (Table 1)
Summary
During chronic lung infections of cystic fibrosis patients Pseudomonas aeruginosa populations undergo extensive evolutionary diversification. Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic lung infections in patients with cystic fibrosis (CF) [1] or non-CF bronchiectasis [2]. Once established as a chronic infection, a P. aeruginosa strain can remain in the lungs of a patient for life, despite frequent use of antibiotic therapy. The pathogen adopts a biofilm lifestyle, with evidence from explanted lungs suggesting the formation of free aggregates rather than surface-attached biofilms [3]. Throughout these long time periods, populations of P. aeruginosa adapt to the CF lung in several. The factors driving and maintaining this diversity, observed in other CF pathogens [21], are poorly understood
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