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Optimised chronic infection models demonstrate that siderophore ‘cheating’ in Pseudomonas aeruginosa is context specific
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Harrison, Freya, McNally, Alan, da Silva, Ana C., Heeb, Stephan and Diggle, Stephen P. (2017) Optimised chronic infection models demonstrate that siderophore ‘cheating’ in Pseudomonas aeruginosa is context specific. The ISME Journal, 11 . pp. 2492-2509. doi:10.1038/ismej.2017.103
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Official URL: http://dx.doi.org/10.1038/ismej.2017.103
Abstract
The potential for siderophore mutants of Pseudomonas aeruginosa to attenuate virulence during infection, and the possibility of exploiting this for clinical ends, have attracted much discussion. This has largely been based on the results of in vitro experiments conducted in iron-limited growth medium, in which siderophore mutants act as social ‘cheats:’ increasing in frequency at the expense of the wild type to result in low-productivity, low-virulence populations dominated by mutants. We show that insights from in vitro experiments cannot necessarily be transferred to infection contexts. First, most published experiments use an undefined siderophore mutant. Whole-genome sequencing of this strain revealed a range of mutations affecting phenotypes other than siderophore production. Second, iron-limited medium provides a very different environment from that encountered in chronic infections. We conducted cheating assays using defined siderophore deletion mutants, in conditions designed to model infected fluids and tissue in cystic fibrosis lung infection and non-healing wounds. Depending on the environment, siderophore loss led to cheating, simple fitness defects, or no fitness effect at all. Our results show that it is crucial to develop defined in vitro models in order to predict whether siderophores are social, cheatable and suitable for clinical exploitation in specific infection contexts.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QR Microbiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||
| Library of Congress Subject Headings (LCSH): | Pseudomonas aeruginosa -- Infections, Siderophores | ||||||
| Journal or Publication Title: | The ISME Journal | ||||||
| Publisher: | Nature Publishing Group | ||||||
| ISSN: | 1751-7362 | ||||||
| Official Date: | 11 July 2017 | ||||||
| Dates: |
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| Volume: | 11 | ||||||
| Page Range: | pp. 2492-2509 | ||||||
| DOI: | 10.1038/ismej.2017.103 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access | ||||||
| Funder: | University of Warwick, University of Nottingham, Natural Environment Research Council (Great Britain) (NERC), International Human Frontier Science Program Organization (IHFSPO) | ||||||
| Grant number: | NE/J007064/1 (NERC), RGY0081/2012 (IHFSPO) | ||||||
| Open Access Version: |
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