Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut.
Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut.
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DOI：
10.1038/ncomms8113
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发表时间：
2015-05-12
影响因子：
16.6
通讯作者：
Vijay-Kumar M
中科院分区：
文献类型：
--
作者：
Singh V;Yeoh BS;Xiao X;Kumar M;Bachman M;Borregaard N;Joe B;Vijay-Kumar M
在肠道炎症反应期间，一些肠道细菌如E.大肠杆菌会大量繁殖并导致疾病在这里，我们证明肠杆菌素（Ent），儿茶酚铁载体释放的E。大肠杆菌中，是一种有效的抑制剂髓过氧化物酶（MPO），杀菌酶的主机。糖基化的Ent（salmochelin）和非儿茶酚铁载体（耶尔森菌素和铁色素）不能抑制MPO活性。大肠过量产生Ent的大肠杆菌突变体（ΔfepA），而不是Ent缺陷的双突变体（ΔaroB/ΔfepA），抑制MPO活性并在发炎的肠道中表现出增强的存活。这种生存优势是由脂质运载蛋白2，铁载体结合宿主蛋白，从ENT介导的抑制中拯救MPO的反调节。光谱分析表明，Ent干扰化合物I [氧合铁，Fe（IV）= O]，并将酶恢复到其天然的三价铁[Fe（III）]状态。这些发现定义了一个基本的机制，通过它E。大肠杆菌在炎症性肠道疾病中超越宿主的先天免疫反应，并获得明显的生存优势。
During an inflammatory response in the gut, some commensal bacteria such as E. coli can thrive and contribute to disease. Here we demonstrate that enterobactin (Ent), a catecholate siderophore released by E. coli, is a potent inhibitor of myeloperoxidase (MPO), a bactericidal enzyme of the host. Glycosylated Ent (salmochelin) and non-catecholate siderophores (yersiniabactin and ferrichrome) fail to inhibit MPO activity. An E. coli mutant (ΔfepA) that overproduces Ent, but not an Ent-deficient double mutant (ΔaroB/ΔfepA), inhibits MPO activity and exhibits enhanced survival in inflamed guts. This survival advantage is counter-regulated by lipocalin 2, a siderophore-binding host protein, which rescues MPO from Ent-mediated inhibition. Spectral analysis reveals that Ent interferes with compound I [oxoiron, Fe(IV) = O] and reverts the enzyme back to its native ferric [Fe(III)] state. These findings define a fundamental mechanism by which E. coli surpasses the host innate immune responses during inflammatory gut diseases and gains a distinct survival advantage.
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影响因子：
11.2
作者：
Chakraborty, Subhankar;Kaur, Sukhwinder;Guha, Sushovan;Batra, Surinder K.
通讯作者：
Batra, Surinder K.
影响因子：
6.7
作者：
Henderson, Jeffrey P.;Crowley, Jan R.;Pinkner, Jerome S.;Walker, Jennifer N.;Tsukayama, Pablo;Stamm, Walter E.;Hooton, Thomas M.;Hultgren, Scott J.
通讯作者：
Hultgren, Scott J.
影响因子：
3.5
作者：
Borregaard, Niels;Cowland, Jack B.
通讯作者：
Cowland, Jack B.
影响因子：
3.6
作者：
Crouch, Marie-Laure V.;Castor, Margaret;Fang, Ferric C.
通讯作者：
Fang, Ferric C.
DOI：
10.1073/pnas.0510847103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Berger, T;Togawa, A;Mak, TW
通讯作者：
Mak, TW