Human Urinary Composition Controls Antibacterial Activity of Siderocalin

J Biol Chem. 2015 Jun 26;290(26):15949-60. doi: 10.1074/jbc.M115.645812. Epub 2015 Apr 10.

Abstract

During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here, we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine.

Keywords: Escherichia coli (E. coli); NGAL; host-pathogen interaction; infectious disease; iron; lipocalin 2; metabolomics; siderocalin; siderophore; urinary tract infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / immunology*
  • Enterobactin / metabolism
  • Escherichia coli / immunology*
  • Escherichia coli / metabolism
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / microbiology
  • Humans
  • Hydrogen-Ion Concentration
  • Iron / metabolism
  • Siderophores / metabolism
  • Urinary Tract Infections / immunology*
  • Urinary Tract Infections / microbiology
  • Urine / chemistry*

Substances

  • Carrier Proteins
  • LCN2 protein, human
  • Siderophores
  • Enterobactin
  • Iron