BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins
BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins
复制标题
DOI：
10.1128/iai.70.10.5390-5403.2002
复制
发表时间：
2002-10-01
影响因子：
3.1
通讯作者：
Connell, TD
中科院分区：
文献类型：
--
作者：
Murphy, ER;Sacco, RE;Connell, TD
铁是大多数生物体的必需元素，必须从当地环境中获取。就致病细菌而言，这一基本元素必须从受感染宿主的体液和组织中获得。在细菌中，为了有效地获取宿主结合的铁，已经进化了各种系统。革兰氏阴性细菌禽波氏杆菌在禽类上呼吸道定植后，在禽类中产生一种与百日咳有惊人相似之处的疾病，百日咳是由人类特有的病原体百日咳杆菌引起的疾病。我们描述了一个由bhuR和6个辅助基因(rhuIR和bhuSTUV)组成的B.avium铁利用基因。对B.avium的遗传操作证实，编码外膜血红素受体的bhur介导了从氯化血红素和血红素蛋白(血红蛋白、肌红蛋白和过氧化氢酶)中有效地获取铁。BHUR包含细菌血红素受体共同的基序，包括一个共同的FRAP结构域，一个NPNL结构域和两个TonB盒。BHUR中存在一个32位氨基酸的N末端片段，这可能是rhuIR调节BHUR表达所必需的，但在其他细菌的血红素受体中不存在。在B.avium外膜上观察到两种形式的BHUR：一种是91 kDa的多肽，大小与预测的成熟蛋白一致；另一种是较小的82 kDa多肽，它缺少91 kDa多肽N端的104个氨基酸。在B.avium中对HEMA中的一个突变进行了改造，以证明该细菌以一种BHHR依赖的方式将血红素运输到细胞质中。通过竞争感染模型，确定了bhur在火鸡雏鸡毒力中的作用。
Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe. The gram-negative bacterium Bordetella avium, upon colonization of the avian upper respiratory tract, produces a disease in birds that has striking similarity to whooping cough, a disease caused by the obligate human pathogen Bordetella pertussis. We describe a B. avium Fe utilization locus comprised of bhuR and six accessory genes (rhuIR and bhuSTUV). Genetic manipulations of B. avium confirmed that bhuR, which encodes a putative outer membrane heme receptor, mediates efficient acquisition of Fe from hemin and hemoproteins (hemoglobin, myoglobin, and catalase). BhuR contains motifs which are common to bacterial heme receptors, including a consensus FRAP domain, an NPNL domain, and two TonB boxes. An N-terminal 32-amino-acid segment, putatively required for rhuIR-dependent regulated expression of bhuR, is present in BhuR but not in other bacterial heme receptors. Two forms of BhuR were observed in the outer membrane of B. avium: a 91-kDa polypeptide consistent in size with the predicted mature protein and a smaller 82-kDa polypeptide which lacks the 104 amino acids found at the N terminus of the 91-kDa form. A mutation in hemA was engineered in B. avium to demonstrate that the bacterium transports heme into the cytoplasm in a BhuR-dependent manner. The role of BhuR in virulence was established in turkey poults by use of a competitive-infection model.