Koh Eun-Ik, Robinson Anne E, Bandara Nilantha, Rogers Buck E, Henderson Jeffrey P
Center for Women's Infectious Diseases Research, Washington University School of Medicine, St. Louis, Missouri, USA.
Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Nat Chem Biol. 2017 Sep;13(9):1016-1021. doi: 10.1038/nchembio.2441. Epub 2017 Jul 24.
Copper plays a dual role as a nutrient and a toxin during bacterial infections. While uropathogenic Escherichia coli (UPEC) strains can use the copper-binding metallophore yersiniabactin (Ybt) to resist copper toxicity, Ybt also converts bioavailable copper to Cu(II)-Ybt in low-copper conditions. Although E. coli have long been considered to lack a copper import pathway, we observed Ybt-mediated copper import in UPEC using canonical Fe(III)-Ybt transport proteins. UPEC removed copper from Cu(II)-Ybt with subsequent re-export of metal-free Ybt to the extracellular space. Copper released through this process became available to an E. coli cuproenzyme (the amine oxidase TynA), linking this import pathway to a nutrient acquisition function. Ybt-expressing E. coli thus engage in nutritional passivation, a strategy of minimizing a metal ion's toxicity while preserving its nutritional availability. Copper acquisition through this process may contribute to the marked virulence defect of Ybt-transport-deficient UPEC.
在细菌感染过程中，铜兼具营养物质和毒素的双重作用。虽然尿路致病性大肠杆菌（UPEC）菌株可利用铜结合金属载体耶尔森菌素（Ybt）来抵抗铜毒性，但在低铜条件下，Ybt还会将生物可利用铜转化为Cu（II）-Ybt。尽管长期以来人们一直认为大肠杆菌缺乏铜导入途径，但我们利用典型的Fe（III）-Ybt转运蛋白在UPEC中观察到了Ybt介导的铜导入。UPEC从Cu（II）-Ybt中去除铜，随后将无金属的Ybt重新输出到细胞外空间。通过这一过程释放的铜可被大肠杆菌铜酶（胺氧化酶TynA）利用，从而将这一导入途径与营养获取功能联系起来。因此，表达Ybt的大肠杆菌参与了营养钝化，这是一种在保留金属离子营养可用性的同时尽量降低其毒性的策略。通过这一过程获取铜可能导致Ybt转运缺陷型UPEC明显的毒力缺陷。
