• Home
  • Search Results
  • Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut.

Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut.

Nature communications (2015-05-13)
Vishal Singh, Beng San Yeoh, Xia Xiao, Manish Kumar, Michael Bachman, Niels Borregaard, Bina Joe, Matam Vijay-Kumar
ABSTRACT

During an inflammatory response in the gut, some commensal bacteria such as E. coli can thrive and contribute to disease. Here we demonstrate that enterobactin (Ent), a catecholate siderophore released by E. coli, is a potent inhibitor of myeloperoxidase (MPO), a bactericidal enzyme of the host. Glycosylated Ent (salmochelin) and non-catecholate siderophores (yersiniabactin and ferrichrome) fail to inhibit MPO activity. An E. coli mutant (ΔfepA) that overproduces Ent, but not an Ent-deficient double mutant (ΔaroB/ΔfepA), inhibits MPO activity and exhibits enhanced survival in inflamed guts. This survival advantage is counter-regulated by lipocalin 2, a siderophore-binding host protein, which rescues MPO from Ent-mediated inhibition. Spectral analysis reveals that Ent interferes with compound I [oxoiron, Fe(IV)=O] and reverts the enzyme back to its native ferric [Fe(III)] state. These findings define a fundamental mechanism by which E. coli surpasses the host innate immune responses during inflammatory gut diseases and gains a distinct survival advantage.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, ≥98%
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, for molecular biology, ≥99%
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Iron(III) chloride, anhydrous, powder, ≥99.99% trace metals basis
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, BioXtra, ≥99%
Sigma-Aldrich
Guaiacol, natural, ≥99%, FG
Sigma-Aldrich
Guaiacol, oxidation indicator
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Hydrogen peroxide solution, 34.5-36.5%
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, BioUltra, for molecular biology, ≥99.0% (AT)
Sigma-Aldrich
Iron(III) chloride, sublimed grade, ≥99.9% trace metals basis
Sigma-Aldrich
o-Dianisidine, peroxidase substrate
Sigma-Aldrich
Iron(III) chloride solution, 0.2 M in 2-methyltetrahydrofuran
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.6%, ReagentPlus®
SAFC
Hexadecyltrimethylammonium bromide