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

Human Urinary Composition Controls Antibacterial Activity of Siderocalin.

Author information

1
From the Division of Infectious Diseases, Department of Medicine, Center for Women's Infectious Disease Research, and.
2
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
3
the Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington 98195.
4
the Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, and.
5
From the Division of Infectious Diseases, Department of Medicine, the Department of Infectious Diseases, Bern University Hospital and University of Bern, 3010 Bern, Switzerland.
6
From the Division of Infectious Diseases, Department of Medicine, Center for Women's Infectious Disease Research, and jhenderson@DOM.wustl.edu.

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

PMID:
25861985
PMCID:
PMC4481200
DOI:
10.1074/jbc.M115.645812
[Indexed for MEDLINE]
Free PMC Article

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