The siderophore yersiniabactin binds copper to protect pathogens during infection.
The siderophore yersiniabactin binds copper to protect pathogens during infection.
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DOI：
10.1038/nchembio.1020
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发表时间：
2012-08
影响因子：
14.8
通讯作者：
Henderson, Jeffrey P.
中科院分区：
文献类型：
--
作者：
Chaturvedi, Kaveri S.;Hung, Chia S.;Crowley, Jan R.;Stapleton, Ann E.;Henderson, Jeffrey P.
细菌病原体分泌化学性质多样的铁螯合剂，称为铁载体，其在体内可能具有其他独特功能。其中，尿路致病性大肠杆菌经常与儿茶酚酸铁载体共同表达与毒力相关的铁载体耶尔森杆菌素（Ybt）。在此，我们使用一种新型质谱筛选方法揭示耶尔森杆菌素也是一种生理上有利的铜（II）配体。在患有大肠杆菌尿路感染的小鼠和人类中对所形成的Cu（II） - Ybt复合物进行直接质谱检测，表明铜结合在感染期间是一种生理相关的体内相互作用。耶尔森杆菌素的表达与人类尿路分离株中较高的铜抗性相对应，表明这种相互作用具有保护作用。化学和遗传学特性表明，耶尔森杆菌素通过螯合宿主来源的铜（II）并防止其通过儿茶酚介导还原为铜（I）来帮助细菌抵抗铜毒性。总之，这些研究揭示了耶尔森杆菌素一种与铁结合不同的新的与毒力相关的功能。
Bacterial pathogens secrete chemically diverse iron chelators called siderophores, which may exert additional distinctive functions in vivo. Among these, uropathogenic E.coli often co-express the virulence-associated siderophore yersiniabactin (Ybt) along with catecholate siderophores. Here we used a novel mass-spectrometric screening approach to reveal that yersiniabactin is also a physiologically favorable copper (II) ligand. Direct mass-spectrometric detection of the resulting Cu(II)-Ybt complex in mice and humans with E. coli urinary tract infections demonstrates copper binding to be a physiologically relevant in vivo interaction during infection. Yersiniabactin expression corresponded to higher copper resistance among human urinary tract isolates, suggesting a protective role for this interaction. Chemical and genetic characterization showed that yersiniabactin helps bacteria resist copper toxicity by sequestering host-derived copper (II) and preventing its catechol-mediated reduction to copper (I). Together, these studies reveal a new virulence-associated function for yersiniabactin that is distinct from iron binding.
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