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首页> 外文期刊>Infection and immunity >Replication of Neisseria meningitidis within Epithelial Cells Requires TonB-Dependent Acquisition of Host Cell Iron
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Replication of Neisseria meningitidis within Epithelial Cells Requires TonB-Dependent Acquisition of Host Cell Iron

机译：脑膜炎奈瑟氏球菌在上皮细胞内的复制需要依赖TonB的宿主细胞铁的获取

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摘要

Neisseria meningitidis (meningococcus [MC]) is able to enter and replicate within epithelial cells. Iron, an essential nutrient for nearly all organisms, is an important determinant in the ability of MC to cause disease; however, its role in MC intracellular replication has not been investigated. We analyzed the growth of MC within the A431 human epithelial cell line and the dependence of this growth on iron uptake. We present evidence here that chelation of iron from infected tissue culture cells with Desferal strongly inhibited intracellular replication of wild-type (wt) MC. We also provide genetic evidence that iron must be acquired by MC from the host cell in order for it to replicate. An hmbR mutant that is unable to use hemoglobin iron and could not grow in tissue culture media without iron supplementation replicated more rapidly within epithelial cells than its wt parent strain. An fbpA mutant that is unable to utilize human transferrin iron or lactoferrin iron replicated normally within cells. In contrast, a tonB mutant could not replicate intracellularly unless infected cultures were supplemented with ferric nitrate. Taken together, these findings strongly suggest that MC intracellular replication requires TonB-dependent uptake of a novel host cell iron source.
机译：脑膜炎奈瑟氏球菌（脑膜炎双球菌[MC]）能够进入并在上皮细胞内复制。铁是几乎所有生物的必需营养素，是MC致病能力的重要决定因素。然而，尚未研究其在MC细胞内复制中的作用。我们分析了A431人上皮细胞系中MC的生长及其对铁摄取的依赖性。我们在这里提供的证据表明，与Desferal感染的组织培养细胞中铁的螯合作用强烈抑制了野生型（wt）MC的细胞内复制。我们还提供了遗传证据，表明铁必须被MC从宿主细胞中获取才能复制。 hmbR 突变体不能使用血红蛋白铁，并且不能在组织培养基中生长，如果不补充铁，其上皮细胞中的复制要比其wt亲本菌株更快。 fbpA 突变体，无法利用正常在细胞内复制的人转铁蛋白铁或乳铁蛋白铁。相反，除非感染的培养物补充硝酸铁，否则 tonB 突变体无法在细胞内复制。综上所述，这些发现强烈表明MC细胞内复制需要依赖TonB的新宿主细胞铁源摄取。

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