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锰转运蛋白MntH是实验感染小鼠中布鲁氏菌2308的关键毒力决定因素。

The manganese transporter MntH is a critical virulence determinant for Brucella abortus 2308 in experimentally infected mice.

作者信息

Anderson Eric S, Paulley James T, Gaines Jennifer M, Valderas Michelle W, Martin Daniel W, Menscher Evan, Brown Timothy D, Burns Colin S, Roop R Martin

机构信息

Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27834, USA.

出版信息

Infect Immun. 2009 Aug;77(8):3466-74. doi: 10.1128/IAI.00444-09. Epub 2009 Jun 1.

Abstract

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 Fe(2+), Zn(2+), Co(2+), or Ni(2+). Consistent with the apparent selectivity of the corresponding gene product, the expression of the mntH gene in B. abortus 2308 is repressed by Mn(2+), but not Fe(2+), 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 Mn(2+) 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.

摘要

布鲁氏菌2308基因组序列中命名为BAB1_1460的基因预计编码锰转运蛋白MntH。对同基因mntH突变体的表型分析表明,MntH是该细菌中唯一的高亲和力锰转运蛋白,但MntH在Fe(2+)、Zn(2+)、Co(2+)或Ni(2+)的转运中未发挥可检测到的作用。与相应基因产物的明显选择性一致,布鲁氏菌2308中mntH基因的表达受Mn(2+)抑制,但不受Fe(2+)抑制,且这种锰反应性表达由一种类似Mur的阻遏物介导。与2308菌株相比,布鲁氏菌mntH突变体MWV15在体外对氧化杀伤的敏感性增加,对这两种菌株中超氧化物歧化酶活性的比较分析表明,亲本菌株需要MntH才能产生野生型水平的锰超氧化物歧化酶SodA。布鲁氏菌mntH突变体在培养的小鼠巨噬细胞和实验感染的C57BL/6小鼠中也表现出极度减毒。这些实验结果表明,由MntH介导的Mn(2+)转运在布鲁氏菌2308的生理学中起重要作用,特别是在其于宿主体内的存活和复制过程中。

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