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
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27834, USA.
Infect Immun. 2009 Aug;77(8):3466-74. doi: 10.1128/IAI.00444-09. Epub 2009 Jun 1.
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.
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。