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

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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
155 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)2492–2509
JournalThe ISME Journal
Volume11
Early online date11 Jul 2017
DOIs
Publication statusPublished - Nov 2017

Fingerprint

Dive into the research topics of 'Optimised chronic infection models demonstrate that siderophore 'cheating' in Pseudomonas aeruginosa is context specific'. Together they form a unique fingerprint.

Cite this