title: Enterococcal Metabolite Cues Facilitate Interspecies Niche Modulation and Polymicrobial Infection.
abstract: 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.
authors.affiliation: Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Damien
authors.initials: D
authors.lastname: Keogh
authors.affiliation: Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Wei Hong
authors.initials: WH
authors.lastname: Tay
authors.affiliation: Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Yao Yong
authors.initials: YY
authors.lastname: Ho
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dale
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 10, Singapore 119074, Singapore.
authors.forename: Siyi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, 28 Medical Drive, Singapore 114756, Singapore.
authors.forename: Shivshankar
authors.initials: S
authors.lastname: Umashankar
authors.affiliation: Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, 28 Medical Drive, Singapore 114756, Singapore.
authors.forename: Rohan B H
authors.initials: RBH
authors.lastname: Williams
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 10, Singapore 119074, Singapore; GERMS and Infectious Disease Group, Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore.
authors.forename: Swaine L
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Dunny
authors.affiliation: Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. Electronic address: kkline@ntu.edu.sg.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kline
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development; D055499:Catheter-Related Infections / Q000382:microbiology; D060085:Coinfection / Q000382:microbiology*; D004195:Disease Models, Animal; D004758:Enterobactin / Q000378:metabolism; D013293:Enterococcus faecalis / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D005260:Female; D007501:Iron / Q000378:metabolism; D008810:Mice, Inbred C57BL; D056265:Microbial Interactions; D050296:Microbial Viability / Q000187:drug effects; D009952:Ornithine / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000382:microbiology; D014946:Wound Infection / Q000382:microbiology
chemical_list: D004758:Enterobactin; D007501:Iron; D009952:Ornithine
keywords: Enterococcus faecalis; Escherichia coli; iron; nutritional immunity; polymicrobial infection; wound infection