Enterobactin Deficiency in a Coliform Mastitis Isolate Decreases Its Fitness in a Murine ModelA Preliminary Host–Pathogen Interaction Study

Authors Organisations
  • Niels Vander Elst(Author)
    Ghent University
  • Koen Breyne(Author)
    Ghent University
    Harvard University
  • Jonas Steenbrugge(Author)
    Ghent University
  • Amanda Gibson(Author)
  • David George Emslie Smith(Author)
    Heriot Watt University
  • Pierre Germon(Author)
    INRAE ​​Val de Loire Centre
  • Dirk Werling(Author)
    Royal Veterinary College
  • Evelyne Meyer(Author)
    Ghent University
Type Article
Original languageEnglish
Article number576583
Number of pages11
JournalFrontiers in Veterinary Science
Publication statusPublished - 09 Nov 2020
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Iron is an essential nutrient for bacterial growth. Therefore, bacteria have evolved chelation mechanisms to acquire iron for their survival. Enterobactin, a chelator with high affinity for ferric iron, is secreted by Escherichia coli and contributes to its improved bacterial fitness. In this preliminary study, we evaluated enterobactin deficiency both in vitro and in vivo in the context of E. coli mastitis. Firstly, we showed that expression of lipocalin 2, a protein produced by the host that is able to both bind and deplete enterobactin, is increased upon E. coli infection in the cow's mastitic mammary gland. Secondly, we demonstrated in vitro that enterobactin deficiency does not alter interleukin (IL)-8 expression in bovine mammary epithelial cells and its associated neutrophil recruitment. However, a significantly increased reactive oxygen species production of these neutrophils was observed. Thirdly, we showed there was no significant difference in bacterial in vitro growth between the enterobactin-deficient mutant and its wild-type counterpart. However, when further explored in a murine model for bovine mastitis, the enterobactin-deficient mutant vs. the wild-type strain revealed a significant reduction of the bacterial load and, consequently, a decrease in pro-inflammatory cytokines (IL-1α,−1β,−4,−6, and−8). A reduced neutrophilic influx was also observed immunohistochemically. These findings therefore identify interference of the enterobactin iron-scavenging mechanism as a potential measure to decrease the fitness of E. coli in the mastitic mammary gland.


  • E. coli mastitis, enterobactin, iron scavenging, siderophores, lipocalin 2 (also known as NGAL)