Abstract
BackgroundPseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. This has led to the suggestion that virulence is a costly attribute in chronic infections. However, previous reports suggest that overproducing (OP) virulent pathotypes can coexist with non-producing mutants in the CF lung for many years. The consequences of such within-patient phenotypic diversity for the success of this pathogen are not fully understood. Here, we provide in-depth quantification of within-host variation in the production of three virulence associated secretions in the Liverpool cystic fibrosis epidemic strain of P. aeruginosa, and investgate the effect of this phenotypic variation on virulence in acute infections of an insect host model.ResultsWithin-patient variation was present for all three secretions (pyoverdine, pyocyanin and LasA protease). In two out of three patients sampled, OP isolates coexisted with under-producing mutants. In the third patient, all 39 isolates were under-producers of all three secretions relative to the transmissible ancestor LESB58. Finally, this phenotypic variation translated into variation in virulence in an insect host model.ConclusionsWithin population variation in the production of P. aeruginosa virulence-associated secretions can lead to high virulence sub-populations persisting in patients with chronic CF infections.
Highlights
Pseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections
We show that within-host phenotypic variation translates into variation in the virulence of acute infections in an insect host model, indicating that population diversity can act as a reservoir for virulent pathotypes
Patients CF03 and CF08 showed similar high within-patient variance in pyoverdine production (CF03 range: 4–116%; CF08 range: 8–113%), driven by the coexistence of isolates that produced pyoverdine at levels at least as high as LESB58, with isolates that produced less than 10% relative to LESB58
Summary
Pseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. Over the course of chronic CF infections, P. aeruginosa undergoes a series of genetic and phenotypic changes in order to adapt to life within the host [5] These typically include loss of virulence factors such as the quorum-sensing regulated pyocyanin, elastase and protease [6], the siderophore pyoverdine [6], as well as emergence of hypermutators [3], conversion to mucoidity [6, 7] increased antibiotic resistance [8] and the loss of motility [6, 9].
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