TY - JOUR
T1 - Human urinary composition controls antibacterial activity of siderocalin
AU - Shields-Cutler, Robin R.
AU - Crowley, Jan R.
AU - Hung, Chia S.
AU - Stapleton, Ann E.
AU - Aldrich, Courtney C.
AU - Marschall, Jonas
AU - Henderson, Jeffrey P.
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
PY - 2015/6/26
Y1 - 2015/6/26
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M115.645812
DO - 10.1074/jbc.M115.645812
M3 - Article
C2 - 25861985
AN - SCOPUS:84940527191
SN - 0021-9258
VL - 290
SP - 15949
EP - 15960
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -