High virulence sub-populations in Pseudomonas aeruginosa long-term cystic fibrosis airway infections.
BACKGROUND
Pseudomonas 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.


RESULTS
Within-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.


CONCLUSIONS
Within 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.
Department of Biology, University of York, Wentworth Way, York, YO10 5DD, UK. siobhan.obrien@york.ac.uk.
Siobhán
http://orcid.org/0000-0002-7588-6825
S
O'Brien
Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool, L69 7B3, UK.
David
D
Williams
Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool, L69 7B3, UK.
Joanne L
JL
Fothergill
Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK.
Steve
S
Paterson
Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool, L69 7B3, UK.
Craig
C
Winstanley
Department of Biology, University of York, Wentworth Way, York, YO10 5DD, UK.|Department of Animal and Plant Sciences, University of Sheffield, Sheffield, S10 2TN, UK.
Michael A
MA
Brockhurst
D000328:Adult; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007313:Insecta / Q000382:microbiology; D008168:Lung / Q000382:microbiology*; D045726:Metalloproteases / Q000032:analysis / Q000378:metabolism; D009154:Mutation; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000209:etiology; D011552:Pseudomonas Infections / Q000209:etiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011710:Pyocyanine / Q000032:analysis / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors / Q000032:analysis
D001426:Bacterial Proteins; D009842:Oligopeptides; D037521:Virulence Factors; C042453:pyoverdin; D011710:Pyocyanine; C548166:LasA protein, Pseudomonas aeruginosa; D045726:Metalloproteases
Cystic fibrosis; LasA protease; Liverpool epidemic strain; Pseudomonas aeruginosa; Public goods secretions; Pyocyanin; Pyoverdine; Virulence