Microbiology
Human Urinary Composition Controls Antibacterial Activity of Siderocalin*,

https://doi.org/10.1074/jbc.M115.645812Get rights and content
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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.

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

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*

This work was supported, in whole or in part, by National Institutes of Health Grants R01DK099534 and P50DK064540 from NIDDK. This work was also supported by National Center for Advancing Translational Sciences Grant UL1TR000448 and the Longer Life Foundation. Mass spectrometry was supported by United States Public Health Service Grants P41RR000954, P30DK020579, P30HL101263 and P30DK056341.

This article was selected as a Paper of the Week.

2

Supported by National Institutes of Health Grant AI070219.

1

Supported by National Institutes of Health Grant T32GM007067-37 and a Monsanto Excellence Fund Graduate Fellowship.

3

Supported by National Institutes of Health Grants U54CK000162 and K12HD001459 and the Barnes-Jewish Hospital Patient Safety and Quality Fellowship Program.