小柯机器人

美国范德比尔特大学Eric P. Skaar和Qiangjun Zhou研究组合作的研究显示艰难梭菌铁质细胞器对抗营养免疫。2023年11月15日出版的《自然》发表了这项成果。

研究人员揭示了艰难梭菌进行细胞内铁生物矿化的过程，并将铁储存在膜结合的铁质体细胞器中，其含有非结晶的磷酸铁生物矿物质。研究发现，铁质体的形成需要膜蛋白（FezA）和P1B6-ATPase转运体（FezB），它们受铁和铁吸收调节因子Fur的抑制，并在铁缺乏向铁过剩过渡期间的铁平衡中发挥重要作用。

此外，正如低温电子断层扫描所揭示，铁质体通常定位在细胞膜附近。研究人员利用两种艰难梭菌感染小鼠模型证明，在发炎的肠道中铁质体系统被激活，以对抗钙蛋白介导的铁螯合作用，这对艰难梭菌感染时其定植和存活非常重要。

据悉，几乎所有生命体都离不开铁，但铁含量过高会产生毒性。为了在宿主体内生存，细菌病原体进化出了铁吸收、储存和解毒策略以维持铁平衡。最近的研究表明，三种革兰氏阴性环境厌氧菌会产生含铁的铁质体颗粒。然而，尚不清楚铁质体是否仅由革兰氏阴性细菌产生。在美国，艰难梭状芽孢杆菌（Clostridioides difficile）是引起院内感染和抗生素相关感染的主要病原体。

附：英文原文

Title: Clostridioides difficile ferrosome organelles combat nutritional immunity

Author: Pi, Hualiang, Sun, Rong, McBride, James R., Kruse, Angela R. S., Gibson-Corley, Katherine N., Krystofiak, Evan S., Nicholson, Maribeth R., Spraggins, Jeffrey M., Zhou, Qiangjun, Skaar, Eric P.

Issue&Volume: 2023-11-15

Abstract: 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.

DOI: 10.1038/s41586-023-06719-9

Source: https://www.nature.com/articles/s41586-023-06719-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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