Shields-Cutler Robin R, Crowley Jan R, Hung Chia S, Stapleton Ann E, Aldrich Courtney C, Marschall Jonas, Henderson Jeffrey P
From the Division of Infectious Diseases, Department of Medicine, Center for Women's Infectious Disease Research, and.
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 2015 Jun 26;290(26):15949-60. doi: 10.1074/jbc.M115.645812. Epub 2015 Apr 10.
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.
在大肠杆菌引起的尿路感染期间，人类泌尿道中的细胞会释放抗菌蛋白铁调素（SCN；也称为脂质运载蛋白2、中性粒细胞明胶酶相关脂质运载蛋白/NGAL或24p3）。SCN可通过螯合与大肠杆菌保守的铁载体肠杆菌素结合的铁离子复合物来干扰大肠杆菌获取铁。在此，我们发现人类尿液成分可逆转这种关系，反而使肠杆菌素对于克服SCN介导的生长限制至关重要。尿液对SCN活性的调控存在广泛的个体差异。我们利用这些差异确定尿液pH升高和芳基代谢物是控制尿液SCN活性的关键生化宿主因素。这些芳基代谢物是肠道微生物代谢的众所周知的产物。总之，这些结果确定了一种先天性抗菌免疫相互作用，该相互作用严重依赖于人类尿液的个体化学特征。
