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Clostridioides difficile ferrosome organelles combat nutritional immunity
Nature ( IF 50.5 ) Pub Date : 2023-11-15 , DOI: 10.1038/s41586-023-06719-9
Hualiang Pi 1, 2, 3 , Rong Sun 4, 5, 6, 7 , James R McBride 8 , Angela R S Kruse 9, 10 , Katherine N Gibson-Corley 2 , Evan S Krystofiak 4 , Maribeth R Nicholson 11 , Jeffrey M Spraggins 4, 9, 10 , Qiangjun Zhou 4, 5, 6, 7 , Eric P Skaar 1, 2
Affiliation  

Iron is indispensable for almost all forms of life but toxic at elevated levels1,2,3,4. To survive within their hosts, bacterial pathogens have evolved iron uptake, storage and detoxification strategies to maintain iron homeostasis1,5,6. Recent studies showed that three Gram-negative environmental anaerobes produce iron-containing ferrosome granules7,8. However, it remains unclear whether ferrosomes are generated exclusively by Gram-negative bacteria. The Gram-positive bacterium Clostridioides difficile is the leading cause of nosocomial and antibiotic-associated infections in the USA9. Here we report that C. difficile undergoes an intracellular iron biomineralization process and stores iron in membrane-bound ferrosome organelles containing non-crystalline iron phosphate biominerals. We found that a membrane protein (FezA) and a P1B6-ATPase transporter (FezB), repressed by both iron and the ferric uptake regulator Fur, are required for ferrosome formation and play an important role in iron homeostasis during transition from iron deficiency to excess. Additionally, ferrosomes are often localized adjacent to cellular membranes as shown by cryo-electron tomography. Furthermore, using two mouse models of C. difficile infection, we demonstrated that the ferrosome system is activated in the inflamed gut to combat calprotectin-mediated iron sequestration and is important for bacterial colonization and survival during C. difficile infection.



中文翻译:


艰难梭菌 铁质细胞器对抗营养免疫



铁几乎是所有生命形式都不可缺少的,但在高水平上有毒1,2,3,4。为了在宿主体内生存,细菌病原体已经进化出铁的吸收、储存和解毒策略,以维持铁稳态1,5,6。最近的研究表明,三种革兰氏阴性环境厌氧菌产生含铁的铁颗粒7,8。然而,目前尚不清楚铁小体是否完全由革兰氏阴性细菌产生。革兰氏阳性菌艰难梭菌是美国医院和抗生素相关感染的主要原因9。在这里,我们报道了艰难梭菌经历细胞内铁生物矿化过程,并将铁储存在含有非结晶磷酸铁生物矿物质的膜结合的铁体细胞器中。我们发现,被铁和铁摄取调节因子 Fur 抑制的膜蛋白 (FezA) 和 P1B6-ATP 酶转运蛋白 (FezB) 是铁小体形成所必需的,并且在从铁缺乏到过量的过渡过程中在铁稳态中发挥重要作用。此外,铁小体通常位于细胞膜附近,如冷冻电子断层扫描所示。此外,使用两种艰难梭菌感染的小鼠模型,我们证明铁小体系统在发炎的肠道中被激活以对抗钙卫蛋白介导的铁隔离,并且对于艰难梭菌感染期间的细菌定植和存活很重要。

更新日期:2023-11-16
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