Open Access Highly Accessed Research article

Sub-inhibitory concentrations of some antibiotics can drive diversification of Pseudomonas aeruginosa populations in artificial sputum medium

Elli A Wright1, Joanne L Fothergill12, Steve Paterson3, Michael A Brockhurst4 and Craig Winstanley1*

Author Affiliations

1 Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK

2 NIHR Biomedical Research Centre in Microbial Disease, University of Liverpool, Liverpool, UK

3 Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7BE, UK

4 Department of Biology, University of York, York, YO10 5DD, UK

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BMC Microbiology 2013, 13:170  doi:10.1186/1471-2180-13-170

Published: 23 July 2013

Abstract

Background

Pseudomonas aeruginosa populations within the cystic fibrosis lung exhibit extensive phenotypic and genetic diversification. The resultant population diversity is thought to be crucial to the persistence of infection and may underpin the progression of disease. However, because cystic fibrosis lungs represent ecologically complex and hostile environments, the selective forces driving this diversification in vivo remain unclear. We took an experimental evolution approach to test the hypothesis that sub-inhibitory antibiotics can drive diversification of P. aeruginosa populations. Replicate populations of P. aeruginosa LESB58 were cultured for seven days in artificial sputum medium with and without sub-inhibitory concentrations of various clinically relevant antibiotics. We then characterised diversification with respect to 13 phenotypic and genotypic characteristics.

Results

We observed that higher population diversity evolved in the presence of azithromycin, ceftazidime or colistin relative to antibiotic-free controls. Divergence occurred due to alterations in antimicrobial susceptibility profiles following exposure to azithromycin, ceftazidime and colistin. Alterations in colony morphology and pyocyanin production were observed following exposure to ceftazidime and colistin only. Diversification was not observed in the presence of meropenem.

Conclusions

Our study indicates that certain antibiotics can promote population diversification when present in sub-inhibitory concentrations. Hence, the choice of antibiotic may have previously unforeseen implications for the development of P. aeruginosa infections in the lungs of cystic fibrosis patients.

Keywords:
Antibiotics; Cystic fibrosis; Population biology; Pseudomonas aeruginosa