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Optimised chronic infection models demonstrate that siderophore ‘cheating’ in Pseudomonas aeruginosa is context specific

Harrison, Freya; McNally, Alan; da Silva, Ana C.; Heeb, Stephan; Diggle, Stephen P.

Authors

Freya Harrison f.harrison@warwick.ac.uk

Alan McNally

Ana C. da Silva

Stephen P. Diggle stephen.diggle@biosci.gatech



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.

Citation

Harrison, F., McNally, A., da Silva, A. C., Heeb, S., & Diggle, S. P. (2017). Optimised chronic infection models demonstrate that siderophore ‘cheating’ in Pseudomonas aeruginosa is context specific. ISME Journal, 11, 2492–2509. doi:10.1038/ismej.2017.103

Journal Article Type Article
Acceptance Date May 17, 2017
Online Publication Date Jul 11, 2017
Publication Date Jul 11, 2017
Deposit Date Oct 5, 2017
Publicly Available Date Nov 30, -0001
Journal ISME Journal
Print ISSN 1751-7362
Electronic ISSN 1751-7362
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 11
Pages 2492–2509
DOI https://doi.org/10.1038/ismej.2017.103
Public URL http://eprints.nottingham.ac.uk/id/eprint/46934
Publisher URL https://www.nature.com/articles/ismej2017103
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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