Human Urinary Composition Controls Siderocalin's Antibacterial Activity.

Shields-Cutler, Robin R; Crowley, Jan R; Hung, Chia S; Stapleton, Ann E; Aldrich, Courtney C; Marschall, Jonas; Henderson, Jeffrey P (2015). Human Urinary Composition Controls Siderocalin's Antibacterial Activity. Journal of biological chemistry, 290(26), pp. 15949-15960. American Society for Biochemistry and Molecular Biology 10.1074/jbc.M115.645812

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Marschall, Jonas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

29 May 2015 09:16

Last Modified:

19 Oct 2015 11:06

Publisher DOI:

10.1074/jbc.M115.645812

PubMed ID:

25861985

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.68086

URI:

https://boris.unibe.ch/id/eprint/68086

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