Passively released heme from hemoglobin and myoglobin is a potential source of nutrient iron for Bordetella bronchiseptica.

Passively released heme from hemoglobin and myoglobin is a potential source of nutrient iron for Bordetella bronchiseptica.
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血红蛋白和肌红蛋白被动释放的血红素是支气管败血博德特氏菌的营养铁的潜在来源。

DOI:
10.1128/iai.00407-07
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发表时间:
2007
影响因子:
3.1
通讯作者:
Connell,TerryD
Connell,TerryD
中科院分区:
医学2区
文献类型:
--
作者:
Mocny,JeffreyC;Olson,JohnS;Connell,TerryD

文献摘要

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支气管败血波氏杆菌的定植导致多种炎性呼吸道感染,包括犬舍咳嗽、猪萎缩性鼻炎和人类百日咳样疾病。为了成功定殖,B.支气管败血症患者必须从受感染的宿主获得铁(Fe)。宿主体内大量的铁被螯合在血红素中,血红素是一种金属卟啉,与血红蛋白和肌红蛋白配位结合。利用血红蛋白和肌红蛋白作为营养铁的来源。支气管败血症需要外膜蛋白BhuR的表达。我们假设氯化血红素是由B.在血红蛋白和/或肌红蛋白中金属卟啉自发丢失后,支气管败血症以BhuR依赖的方式发生。隔离实验表明,与血红蛋白或肌红蛋白的直接接触并不需要支持B的生长。支气管败血症在铁限制的环境中。突变的肌红蛋白,每一个表现出不同的亲和力血红素,被用来证明B。支气管败血症与血红素从血红素蛋白中丢失的速率直接相关。最后,大肠杆菌表达重组BhuR有能力从溶液中去除氯化血红素。总的来说,这些实验为BhuR是氯化血红素受体和B.支气管败血症类似地在感染期间在从血红蛋白和/或肌红蛋白被动损失金属卟啉之后获得血红素。这些结果也表明,血红素和肌红蛋白的自发性血红素损失可能是许多病原菌获得血红素和血红素结合铁的共同机制。
Colonization byBordetella bronchisepticaresults in a variety of inflammatory respiratory infections, including canine kennel cough, porcine atrophic rhinitis, and a whooping cough-like disease in humans. For successful colonization,B. bronchisepticamust acquire iron (Fe) from the infected host. A vast amount of Fe within the host is sequestered within heme, a metalloporphyrin which is coordinately bound in hemoglobin and myoglobin. Utilization of hemoglobin and myoglobin as sources of nutrient Fe byB. bronchisepticarequires expression of BhuR, an outer membrane protein. We hypothesize that hemin is acquired byB. bronchisepticain a BhuR-dependent manner after spontaneous loss of the metalloporphyrin from hemoglobin and/or myoglobin. Sequestration experiments demonstrated that direct contact with hemoglobin or myoglobin was not required to support growth ofB. bronchisepticain an Fe-limiting environment. Mutant myoglobins, each exhibiting a different affinity for heme, were employed to demonstrate that the rate of growth ofB. bronchisepticawas directly correlated with the rate at which heme was lost from the hemoprotein. Finally,Escherichia colicells expressing recombinant BhuR had the capacity to remove hemin from solution. Collectively, these experiments provided strong experimental support for the model that BhuR is a hemin receptor andB. bronchisepticalikely acquires heme during infection after passive loss of the metalloporphyrin from hemoglobin and/or myoglobin. These results also suggest that spontaneous hemin loss by hemoglobin and myoglobin may be a common mechanism by which many pathogenic bacteria acquire heme and heme-bound Fe.