Enterococcal Metabolite Cues Facilitate Interspecies Niche Modulation and Polymicrobial Infection

Damien Keogh, Wei Hong Tay, Yao Yong Ho, Jennifer L Dale, Siyi Chen, Shivshankar Umashankar, Rohan B.H. Williams, Swaine L. Chen, Gary M Dunny, Kimberly A. Kline

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Enterococcus faecalis is frequently associated with polymicrobial infections of the urinary tract, indwelling catheters, and surgical wound sites. E. faecalis co-exists with Escherichia coli and other pathogens in wound infections, but mechanisms that govern polymicrobial colonization and pathogenesis are poorly defined. During infection, bacteria must overcome multiple host defenses, including nutrient iron limitation, to persist and cause disease. In this study, we investigated the contribution of E. faecalis to mixed-species infection when iron availability is restricted. We show that E. faecalis significantly augments E. coli biofilm growth and survival in vitro and in vivo by exporting L-ornithine. This metabolic cue facilitates E. coli biosynthesis of the enterobactin siderophore, allowing E. coli growth and biofilm formation in iron-limiting conditions that would otherwise restrict its growth. Thus, E. faecalis modulates its local environment by contributing growth-promoting cues that allow co-infecting organisms to overcome iron limitation and promotes polymicrobial infections.

Original languageEnglish (US)
Pages (from-to)493-503
Number of pages11
JournalCell Host and Microbe
Issue number4
StatePublished - Oct 12 2016

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation and Ministry of Education Singapore under its Research Centre of Excellence Programme. D.K., W.H.T., Y.Y.H., and K.A.K. were supported by the National Research Foundation under its Singapore NRF Fellowship programme (NRF-NRFF2011-11), by the Ministry of Education Singapore under its Tier 2 programme (MOE2014-T2-2-124), and by NIH NIAID R21 AI126023-01. S.C. and S.L.C. were supported by NRF-RF2010-10. We thank Daniela Moses and colleagues for performing library preparation and RNA-seq; Sanjay Swarup, Victor Nesati, and colleagues for conducting the metabolomics survey; Jeff Henderson and Scott Hultgren for providing E. coli siderophore mutants; and Kenneth Beckman and colleagues for sequencing of the E. faecalis transposon library.

Publisher Copyright:
© 2016 Elsevier Inc.


  • Enterococcus faecalis
  • Escherichia coli
  • iron
  • nutritional immunity
  • polymicrobial infection
  • wound infection


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