Iron-containing ferrosome granules have previously been discovered in Gram-negative environmental anaerobes, however, their presence in Gram-positive bacteria has not been previously documented. Now, a team of researchers has discovered that Clostridioides difficile (C. diff) produces ferrosomes and that these structures are important for infection in an animal model.

先前已在革兰氏阴性环境厌氧菌中发现含铁的铁体颗粒，然而，它们在革兰氏阳性细菌中的存在尚未有过记载。现在，一组研究人员发现艰难梭菌（C.diff）产生铁体，这些结构对于动物模型中的感染很重要。

In addition, the findings are a rare demonstration of a membrane-bound structure inside a pathogenic bacterium..

此外，这些发现是致病细菌内膜结合结构的罕见证明。。

This work is published in Nature in the paper, “Clostridioides difficile ferrosome organelles combat nutritional immunity.”

这项工作发表在Nature的论文中，“艰难梭菌铁体细胞器对抗营养免疫”

“The emerging idea that bacteria do compartmentalize biochemical processes in a way similar to eukaryotic cells really flips the field of microbiology on its head,” said Eric Skaar, PhD, professor of pathology and director of the Vanderbilt Institute for Infection, Immunology, and Inflammation.

范德比尔特感染，免疫学研究所病理学教授兼主任埃里克·斯卡尔（Eric Skaar）博士说：“新出现的细菌以类似于真核细胞的方式划分生物化学过程的想法确实改变了微生物学领域。炎症。

“The best way to look for the accumulation of elements in a small space like a cell is with a method called STEM-EDS, which has not commonly been used for biological samples,” Skaar said. “We were fortunate to have access to a STEM-EDS instrument and collaborators at Vanderbilt Institute of Nanoscale Science and Engineering (VINSE) and we quickly proved that there was an accumulation of iron ‘dots’ within the bacterium.”.

Skaar说：“寻找像细胞这样的小空间中元素积累的最佳方法是使用一种称为STEM-EDS的方法，这种方法通常不用于生物样品。“我们很幸运能够获得范德比尔特纳米科学与工程研究所（VINSE）的STEM-EDS仪器和合作者，我们很快证明细菌内存在铁'点'的积累。”。

C. diff causes about 500,000 infections and more than 29,000 deaths in the United States each year, according to the Centers for Disease Control and Prevention, and treatment options are limited. People taking antibiotics that disrupt the healthy microbes in the gut are at increased risk for C. diff infection, which causes diarrhea and colitis.

C、 根据疾病控制和预防中心的数据，diff每年在美国造成约500000例感染和超过29000例死亡，治疗方案有限。服用抗生素破坏肠道健康微生物的人患C.diff感染的风险增加，导致腹泻和结肠炎。

New strategies for treating this urgent public health threat are needed, Skaar said..

Skaar说，需要采取新的策略来治疗这种紧急的公共卫生威胁。。

The researchers found that two genes (fezA and fezB), which are similar to those in environmental bacteria, were required for ferrosome formation. More specifically, they write, “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.”.

研究人员发现，两种基因（fezA和fezB）与环境细菌中的基因相似，是形成铁体所必需的。更具体地说，他们写道，“膜蛋白（FezA）和P1B6 ATP酶转运蛋白（FezB），被铁和铁吸收调节剂Fur抑制，是铁体形成所必需的，并且在从缺铁过渡到过量期间在铁稳态中起重要作用。”。

They showed that ferrosomes are required for C. diff to fully colonize and cause disease in an animal model and that ferrosomes were even more important for C. diff infection in a model of inflammatory bowel disease. These findings demonstrate that these iron-containing structures help the bacterium combat “nutritional immunity”—the host response of producing proteins to bind iron and attempt to starve the pathogen..

他们表明，C.diff需要铁体在动物模型中完全定植并引起疾病，并且在炎症性肠病模型中铁体对于C.diff感染更为重要。这些发现表明，这些含铁结构有助于细菌抵抗“营养免疫”-产生蛋白质以结合铁并试图使病原体饥饿的宿主反应。。

They then used cryogenic electron microscopy (cryo-EM) and cryo-tomography to show that the ferrosome structures were encased in a membrane, classifying them as organelles.

然后，他们使用低温电子显微镜（cryo-EM）和冷冻断层扫描显示铁体结构被包裹在膜中，将它们分类为细胞器。

The results “establish ferrosome formation and all the factors involved in ferrosome formation as potential targets for new antibacterial drugs against an important infectious disease,” Skaar said. “Anytime we find new factors involved in host-pathogen interactions and show that they’re important for infection, that opens entirely new opportunities to make classes of antibacterial drugs that have not existed before.

Skaar说，结果“建立了铁体的形成和铁体形成中涉及的所有因素，作为针对重要传染病的新型抗菌药物的潜在靶标”。“每当我们发现涉及宿主-病原体相互作用的新因素并表明它们对感染很重要时，这就为制造以前不存在的抗菌药物开辟了全新的机会。

That is especially important in the face of rising antimicrobial resistance that we’re seeing globally.”.

面对我们在全球范围内看到的抗菌素耐药性上升，这一点尤为重要。”。

In future studies, the researchers plan to explore how ferrosomes are formed, whether other gut pathogens produce ferrosomes, and whether these structures might be shared in the gut as a source of iron. Skaar is also particularly interested in pursuing the emerging area of bacterial organelles.

在未来的研究中，研究人员计划探索如何形成铁体，其他肠道病原体是否产生铁体，以及这些结构是否可能在肠道中作为铁源共享。Skaar也特别有兴趣追求细菌细胞器的新兴领域。

“We think our study is a rare demonstration of an organelle in a pathogenic bacterium,” he said. “Now we want to know if there are other subcellular compartments in bacteria that we’re interested in that could teach us about how these cells perform various physiologic processes.”

他说：“我们认为我们的研究是致病细菌中细胞器的罕见证明。”。“现在我们想知道细菌中是否还有其他我们感兴趣的亚细胞区室可以教我们这些细胞如何进行各种生理过程。”

Clostridium difficileCryo-electron microscopyMembrane proteinsNovel targets identificationOrganelle

艰难梭菌电子显微镜膜蛋白新靶标鉴定有机体