The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection.
The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection.
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DOI：
10.1038/srep35285
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发表时间：
2016-10-21
影响因子：
4.6
通讯作者：
Schembri MA
中科院分区：
文献类型：
--
作者：
Shepherd M;Achard ME;Idris A;Totsika M;Phan MD;Peters KM;Sarkar S;Ribeiro CA;Holyoake LV;Ladakis D;Ulett GC;Sweet MJ;Poole RK;McEwan AG;Schembri MA
一氧化氮（NO）是中性粒细胞和巨噬细胞在感染反应中产生的一种有毒自由基。尿路致病性大肠杆菌（UPEC）诱导多种防御机制响应NO，包括直接NO解毒（Hmp, NorVW, NrfA），铁硫簇修复（YtfE）和NO耐受细胞色素bd-I呼吸氧化酶（CydAB）的表达。目前的研究量化了这些系统在感染期间对upc生长和存活的相对贡献。黄血红蛋白Hmp和细胞色素bd-I的缺失引起对no介导的生长抑制的最大敏感性，而除了质周亚硝酸盐还原酶NrfA外，所有这些都能保护巨噬细胞免受中性粒细胞的杀伤，并促进活化巨噬细胞的存活。有趣的是，细胞色素bd-I呼吸氧化酶是小鼠模型2天后唯一增加UPEC存活的系统，这表明在亚硝化应激条件下维持有氧呼吸是宿主定植的关键因素。这些发现表明，虽然UPEC已经获得了一系列专门的机制来逃避亚硝化应激，但细胞色素bd-I呼吸氧化酶是微氧条件下NO耐受性和宿主定植的主要贡献者。因此，这种呼吸道复合体对于尿路感染期间高细菌负荷的积累具有重要意义。
Nitric oxide (NO) is a toxic free radical produced by neutrophils and macrophages in response to infection. Uropathogenic Escherichia coli (UPEC) induces a variety of defence mechanisms in response to NO, including direct NO detoxification (Hmp, NorVW, NrfA), iron-sulphur cluster repair (YtfE), and the expression of the NO-tolerant cytochrome bd-I respiratory oxidase (CydAB). The current study quantifies the relative contribution of these systems to UPEC growth and survival during infection. Loss of the flavohemoglobin Hmp and cytochrome bd-I elicit the greatest sensitivity to NO-mediated growth inhibition, whereas all but the periplasmic nitrite reductase NrfA provide protection against neutrophil killing and promote survival within activated macrophages. Intriguingly, the cytochrome bd-I respiratory oxidase was the only system that augmented UPEC survival in a mouse model after 2 days, suggesting that maintaining aerobic respiration under conditions of nitrosative stress is a key factor for host colonisation. These findings suggest that while UPEC have acquired a host of specialized mechanisms to evade nitrosative stresses, the cytochrome bd-I respiratory oxidase is the main contributor to NO tolerance and host colonisation under microaerobic conditions. This respiratory complex is therefore of major importance for the accumulation of high bacterial loads during infection of the urinary tract.
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影响因子：
64.8
作者：
Kers, JA;Wach, MJ;Loria, R
通讯作者：
Loria, R
影响因子：
3.1
作者：
Allsopp, Luke P.;Totsika, Makrina;Schembri, Mark A.
通讯作者：
Schembri, Mark A.
影响因子：
3.7
作者：
Forde BM;Ben Zakour NL;Stanton-Cook M;Phan MD;Totsika M;Peters KM;Chan KG;Schembri MA;Upton M;Beatson SA
通讯作者：
Beatson SA
影响因子：
6.4
作者：
Ben Zakour NL;Alsheikh-Hussain AS;Ashcroft MM;Khanh Nhu NT;Roberts LW;Stanton-Cook M;Schembri MA;Beatson SA
通讯作者：
Beatson SA
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL