Institut Pasteur, Infection Bactériennes Invasives, Dept. Infection et Epidémiologie, Paris, France.
PLoS Pathog. 2011 Sep;7(9):e1002261. doi: 10.1371/journal.ppat.1002261. Epub 2011 Sep 29.
Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) are adapted to different environments within their human host. If the basis of this difference has not yet been fully understood, previous studies (including our own data) have reported that, unlike Ng, Nm tolerates high manganese concentrations. As transition metals are essential regulators of cell growth and host pathogen interactions, we aimed to address mechanisms of Nm Mn²⁺ tolerance and its pathogenic consequences. Using bioinformatics, gene deletion and heterologous expression we identified a conserved bacterial manganese resistance factor MntX (formerly YebN). The predicted structure suggests that MntX represents a new family of transporters exporting Mn. In the Neisseria genus, this exporter is present and functional in all Nm isolates but it is mutated in a majority of Ng strains and commonly absent in nonpathogenic species. In Nm, Mn²⁺ export via MntX regulates the intracellular Mn/Fe ratio and protects against manganese toxicity that is exacerbated in low iron conditions. MntX is also important for N. meningitidis to resist killing by human serum and for survival in mice blood during septicemia. The present work thus points to new clues about Mn homeostasis, its interplay with Fe metabolism and the influence on N. meningitidis physiology and pathogenicity.
脑膜炎奈瑟菌（Nm）和淋病奈瑟菌（Ng）在其人类宿主的不同环境中适应。如果尚未完全了解这种差异的基础，以前的研究（包括我们自己的数据）已经报告说，与 Ng 不同，Nm 耐受高锰浓度。由于过渡金属是细胞生长和宿主病原体相互作用的重要调节剂，我们旨在解决 Nm Mn²⁺耐受的机制及其致病后果。我们使用生物信息学、基因缺失和异源表达鉴定了一种保守的细菌锰抗性因子 MntX（以前称为 YebN）。预测的结构表明，MntX 代表一种新的转运体家族，可将 Mn 输出。在奈瑟菌属中，这种外排体存在于所有 Nm 分离株中且具有功能，但在大多数 Ng 菌株中发生突变，在非致病性物种中通常不存在。在 Nm 中，通过 MntX 进行的 Mn²⁺外排可调节细胞内 Mn/Fe 比，并防止在低铁条件下加剧的锰毒性。MntX 对于 N. meningitidis 抵抗人血清的杀伤以及在败血症期间在小鼠血液中存活也很重要。因此，目前的工作为 Mn 动态平衡、其与 Fe 代谢的相互作用以及对 N. meningitidis 生理学和致病性的影响提供了新的线索。
