The Manganese Transporter MntH Is a Critical Virulence Determinant for Brucella abortus 2308 in Experimentally Infected Mice

The Manganese Transporter MntH Is a Critical Virulence Determinant for Brucella abortus 2308 in Experimentally Infected Mice
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DOI:
10.1128/iai.00444-09
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发表时间:
2009-08-01
影响因子:
3.1
通讯作者:
Roop, R. Martin, II
Roop, R. Martin, II
中科院分区:
医学2区
文献类型:
--
作者:
Anderson, Eric S.;Paulley, James T.;Roop, R. Martin, II

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预测在流产布鲁氏菌2308基因组序列中命名为BAB1_1460的基因编码锰转运蛋白MntH。表型分析的同基因mntH突变体表明,MntH是唯一的高亲和力锰转运蛋白在这种细菌,但MntH不发挥可检测的作用,在运输的Fe 2+,Zn 2+,Co 2+,或Ni 2+。与相应基因产物的表观选择性一致,mntH基因在B.流产2308被Mn ~(2+)抑制,但不被Fe ~(2+)抑制,并且这种Mn响应性表达由Mur样抑制物介导。B。与菌株2308相比,牛流产杆菌mntH突变体MWV 15在体外表现出对氧化杀伤的敏感性增加,并且对这两种菌株中存在的超氧化物歧化酶活性的比较分析表明,亲本菌株需要MntH以使其锰超氧化物歧化酶SodA达到野生型水平。B。流产mntH突变体在培养的鼠巨噬细胞和实验感染的C57 BL/6小鼠中也表现出极端减毒。这些实验结果表明MntH介导的Mn 2+转运在B的生理过程中起着重要的作用。流产病毒2308,特别是在其细胞内的生存和复制的主机。
The gene designated BAB1_1460 in the Brucella abortus 2308 genome sequence is predicted to encode the manganese transporter MntH. Phenotypic analysis of an isogenic mntH mutant indicates that MntH is the sole high-affinity manganese transporter in this bacterium but that MntH does not play a detectable role in the transport of Fe2+, Zn2+, Co2+, or Ni2+. Consistent with the apparent selectivity of the corresponding gene product, the expression of the mntH gene in B. abortus 2308 is repressed by Mn2+, but not Fe2+, and this Mn-responsive expression is mediated by a Mur-like repressor. The B. abortus mntH mutant MWV15 exhibits increased susceptibility to oxidative killing in vitro compared to strain 2308, and a comparative analysis of the superoxide dismutase activities present in these two strains indicates that the parental strain requires MntH in order to make wild-type levels of its manganese superoxide dismutase SodA. The B. abortus mntH mutant also exhibits extreme attenuation in both cultured murine macrophages and experimentally infected C57BL/6 mice. These experimental findings indicate that Mn2+ transport mediated by MntH plays an important role in the physiology of B. abortus 2308, particularly during its intracellular survival and replication in the host.