Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG.
Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG.
复制标题
金黄色葡萄球菌血红素生物合成和获取途径通过血红素单加氧酶 IsdG 连接。
DOI：
10.1111/mmi.14060
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发表时间：
2018
影响因子：
3.6
通讯作者：
Videira MAM
中科院分区：
文献类型：
--
作者：
Videira MAM
血红素是绝大多数生命系统中央代谢途径的重要辅助因子。原核生物通过血红素生物合成途径获得血红素，有些还利用血红素摄取系统，但仍不清楚它们如何平衡血红素需求与游离血红素有毒的悖论。在这里，使用模型病原体金黄色葡萄球菌，我们报告了 IsdG（血红素摄取系统中的两种血红素加氧酶之一）通过内部血红素生物合成途径抑制血红素的形成。更具体地说，我们表明 IsdG 降低亚铁螯合酶的活性，并且这两种蛋白质在体外和体内都相互作用。此外，生物信息学分析表明，大量含有血红素生物合成途径的生物体具有 IsdG 同源物，并且同时具有生物合成和摄取系统的生物体至少具有两种血红素加氧酶。我们得出结论，IsdG 样蛋白通过耦合这两种途径来控制细胞内血红素水平。因此IsdG是治疗S的靶标。金黄色葡萄球菌感染。
Haem is an essential cofactor in central metabolic pathways in the vast majority of living systems. Prokaryotes acquire haem via haem biosynthesis pathways, and some also utilize haem uptake systems, yet it remains unclear how they balance haem requirements with the paradox that free haem is toxic. Here, using the model pathogenStaphylococcus aureus, we report that IsdG, one of two haem oxygenase enzymes in the haem uptake system, inhibits the formation of haem via the internal haem biosynthesis route. More specifically, we show that IsdG decreases the activity of ferrochelatase and that the two proteins interact bothin vitroandin vivo. Further, a bioinformatics analysis reveals that a significant number of haem biosynthesis pathway containing organisms possess an IsdG‐homologue and that those with both biosynthesis and uptake systems have at least two haem oxygenases. We conclude that IsdG‐like proteins control intracellular haem levels by coupling the two pathways. IsdG is thus a target for the treatment ofS. aureusinfections.