Manganese transporters regulate the resumption of replication in hydrogen peroxide-stressed Escherichia coli
Manganese transporters regulate the resumption of replication in hydrogen peroxide-stressed Escherichia coli
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DOI：
10.1007/s10534-023-00523-8
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发表时间：
2023-07-26
期刊：
影响因子：
3.5
通讯作者：
Courcelle，Charmain T.
中科院分区：
文献类型：
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作者：
Wang，Natalie E. E.;Courcelle，Eleanor J. J.;Courcelle，Charmain T.
经过过氧化氢处理后，二价铁 (Fe2+) 被氧化为其三价铁形式 (Fe3+)，将其从含铁蛋白质中剥离并使其失活。许多单核铁酶可以被锰重金属化以恢复功能，而其他酶则专门利用锰作为辅助因子，具有多余的活性来补偿铁耗尽的对应物。 DNA 复制依赖于一种或多种铁依赖性蛋白质，因为过氧化氢存在下合成会减弱，需要培养基中的锰才能恢复。在这里，我们表明锰转运蛋白调节大肠杆菌氧化挑战后恢复复制的能力。主要锰输入蛋白 MntH 的缺失会损害恢复复制的能力；而删除锰输出蛋白 MntP 或转运调节蛋白 MntR 则可显着提高恢复率。即使缺乏维持铁稳态的毛皮，不受管制的锰进口也促进了复苏。类似地，inoxyR突变体的复制也没有恢复，其在过氧化氢应激后不能上调锰的输入。总而言之，这些结果确定了锰转运在氧化应激后恢复复制中的核心作用。
Following hydrogen peroxide treatment, ferrous iron (Fe2+) is oxidized to its ferric form (Fe3+), stripping it from and inactivating iron-containing proteins. Many mononuclear iron enzymes can be remetallated by manganese to restore function, while other enzymes specifically utilize manganese as a cofactor, having redundant activities that compensate for iron-depleted counterparts. DNA replication relies on one or more iron-dependent protein(s) as synthesis abates in the presence of hydrogen peroxide and requires manganese in the medium to resume. Here, we show that manganese transporters regulate the ability to resume replication following oxidative challenge inEscherichia coli. The absence of the primary manganese importer, MntH, impairs the ability to resume replication; whereas deleting the manganese exporter, MntP, or transporter regulator, MntR, dramatically increases the rate of recovery. Unregulated manganese import promoted recovery even in the absence of Fur, which maintains iron homeostasis. Similarly, replication was not restored inoxyRmutants, which cannot upregulate manganese import following hydrogen peroxide stress. Taken together, the results define a central role for manganese transport in restoring replication following oxidative stress.