Iron Deficiency Modulates Metabolic Landscape of Bacteroidetes Promoting Its Resilience during Inflammation.
Iron Deficiency Modulates Metabolic Landscape of Bacteroidetes Promoting Its Resilience during Inflammation.
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DOI：
10.1128/spectrum.04733-22
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发表时间：
2023-08-17
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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细菌必须在低铁条件下生存，以适应宿主的营养免疫。由于对拟杆菌门的铁刺激的了解很少，我们检查了口腔（牙龈卟啉单胞菌和中间普雷沃氏菌）和肠道（拟杆菌门）代表它们适应铁缺乏和铁充满条件的能力。我们的转录组学和比较基因组学分析表明，许多铁调控机制在门内是保守的。它们包括在低铁条件下上调的基因，如fldA（黄氧还蛋白）、hmu（血红素摄取操纵子）和编码ABC转运蛋白的位点。下调基因分别为frd（铁氧还蛋白）、rbr（红毛赤苷）、sdh（琥珀酸脱氢酶/富马酸还原酶）、vor（氧葡萄糖酸氧化还原酶/脱氢酶）和pfor（丙酮酸：铁氧还蛋白/黄氧还蛋白氧化还原酶）。一些属特异性的机制，如编码碳水化合物代谢的B. thetaiotaomicron和编码异种铁载体利用的xusABC也被确定。虽然在我们的研究中测试的所有细菌都有编码亚硝酸盐还原的nrfAH操纵子，并且能够降低培养基中存在的亚硝酸盐水平，但该操纵子的表达仅在b.s thetaiotaomicron中依赖铁。值得注意的是，我们发现在我们的研究中发现的调节基因与b.s thetaiotaomicron结肠炎研究之间存在显著的重叠（W. Zhu， M. G. Winter， L. Spiga， E. R. Hughes等人，Cell Host microbiology 27:37 76 - 388, 2020, http://dx.doi.org/10.1016/j.chom.2020.01.010）。在口腔细菌属中，许多常见的受铁调控的基因也受铁调控。总的来说，这项工作指出铁是使细菌在宿主中存活的主要调节剂，并为更广泛地研究拟杆菌门中铁稳态的分子机制铺平了道路。拟杆菌门是一种重要的厌氧菌群，存在于口腔和肠道微生物群中。虽然铁是大多数生物必需的营养物质，但在这类细菌中，适应铁水平变化的分子机制尚不清楚。我们通过检查牙龈卟啉单胞菌和中间普雷沃氏菌（都属于口腔微生物组）和太古细菌（属于肠道微生物组）的转录组反应来定义拟杆菌门的铁刺激。我们的研究结果表明，许多铁调控的操作子在这三个属中是共享的。此外，通过生物信息学分析，我们发现体外研究与结肠炎研究的转录组学数据之间存在显著的重叠，从而强调了我们工作的生物学意义。确定拟杆菌门的铁依赖性刺激有助于确定铁依赖性调节的分子机制，并更好地了解人类宿主中厌氧菌的持久性。
Bacteria have to persist under low iron conditions in order to adapt to the nutritional immunity of a host. Since the knowledge of iron stimulon of Bacteroidetes is sparse, we examined oral (Porphyromonas gingivalis and Prevotella intermedia) and gut (Bacteroides thataiotaomicron) representatives for their ability to adapt to iron deplete and iron replete conditions. Our transcriptomics and comparative genomics analysis show that many iron-regulated mechanisms are conserved within the phylum. They include genes upregulated in low iron, as follows: fldA (flavodoxin), hmu (hemin uptake operon), and loci encoding ABC transporters. Downregulated genes were frd (ferredoxin), rbr (rubrerythrin), sdh (succinate dehydrogenase/fumarate reductase), vor (oxoglutarate oxidoreductase/dehydrogenase), and pfor (pyruvate:ferredoxin/flavodoxin oxidoreductase). Some genus-specific mechanisms, such as the sus of B. thetaiotaomicron coding for carbohydrate metabolism and the xusABC coding for xenosiderophore utilization were also identified. While all bacteria tested in our study had the nrfAH operon coding for nitrite reduction and were able to reduce nitrite levels present in culture media, the expression of the operon was iron dependent only in B. thetaiotaomicron. It is noteworthy that we identified a significant overlap between regulated genes found in our study and the B. thetaiotaomicron colitis study (W. Zhu, M. G. Winter, L. Spiga, E. R. Hughes et al., Cell Host Microbe 27:376–388, 2020, http://dx.doi.org/10.1016/j.chom.2020.01.010). Many of those commonly regulated genes were also iron regulated in the oral bacterial genera. Overall, this work points to iron being the master regulator enabling bacterial persistence in the host and paves the way for a more generalized investigation of the molecular mechanisms of iron homeostasis in Bacteroidetes. IMPORTANCE Bacteroidetes are an important group of anaerobic bacteria abundant both in the oral and gut microbiomes. Although iron is a required nutrient for most living organisms, the molecular mechanisms of adaptation to the changing levels of iron are not well known in this group of bacteria. We defined the iron stimulon of Bacteroidetes by examination of the transcriptomic response of Porphyromonas gingivalis and Prevotella intermedia (both belong to the oral microbiome) and Bacteroidetes thetaiotaomicron (belongs to the gut microbiome). Our results indicate that many of the iron-regulated operons are shared among the three genera. Furthermore, using bioinformatics analysis, we identified a significant overlap between our in vitro studies and transcriptomic data derived from a colitis study, thus underscoring the biological significance of our work. Defining the iron-dependent stimulon of Bacteroidetes can help to identify the molecular mechanisms of iron-dependent regulation as well as better understand the persistence of the anaerobes in the human host.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
4
作者：
Comstock, LE;Coyne, MJ
通讯作者：
Coyne, MJ
影响因子：
4.6
作者：
Boyer, Emile;Le Gall-David, Sandrine;Meuric, Vincent
通讯作者：
Meuric, Vincent
促炎细胞因子白细胞介素 6 诱导的铁调素，是牙周炎相关炎症性贫血的关键介质
影响因子：
3.5
作者：
Han, Ye;Huang, Wenxue;Hou, Jianxia
通讯作者：
Hou, Jianxia
影响因子：
5.2
作者：
Buckel W;Thauer RK
通讯作者：
Thauer RK